Overview of crystallography in Japan (1913 – 1980) 

Modern crystallography in Japan started right after Laue’s discovery of diffraction of X-rays by crystals (1912), and many valuable achievements were realized during those early years. To our regret, most of them were not recognized outside of Japan. This article will present an outline of crystallography in Japan, especially crystal structure determination, from its advent to approximately 1980. The reviewer apologizes that he cannot fully review research in physics and mineralogy since he is a chemist.

The early years of Crystallography to about 1945

In 1913, T. Terada tried X-ray experiments using a rock salt crystal and a fluorescent screen in a dark room. He observed several diffraction spots and that they moved according to the movement of the crystal. He explained this phenomenon as reflection of the incident X-ray beam from the atomic net planes in the crystal (Nature 91, 135 (1913)). His work paralleled that reported by Bragg (Nature 91, 557 (1913)).
S. Nishikawa, stimulated by Terada’s experiment, began X-ray diffraction studies with Pt white X-rays of (i) fibrous materials such as cotton, silk, and asbestos, (ii) minerals such as mica and talc, and (iii) crystalline powders of fluorite and zinc blende. He found that materials of group (i) were aggregates of micro crystals having a common (fiber) axis, group (ii) were stacked aggregates of thin leafy crystals, and group (iii) were randomly oriented powdered crystals (Proc. Math. Phys. Soc. Tokyo, 7, 131 (1913)). He was a pioneer in the area of X-ray studies of structures of complex compounds. Nishikawa (1915) then studied the structure of spinel, using Laue photographs with space group theory. This was the first case in which space group theory was applied to crystal structure determination. Nishikawa and K. Matsukawa (1928) verified, by experiments on zinc blende, the breakdown of Friedel’s law for crystals containing atoms which anomalously dispersed incident X-rays. This work was reported two years earlier than that of Coster, Knol, and Prins (1930). In 1922, Nishikawa organized a crystallography research group that used both X-ray and electron diffraction in the Institute for Physical and Chemical Research (Tokyo). I. Nitta, a member of the group, studied the crystal structure of pentaerythritol C(CH₂OH)₄ to establish tetrahedral carbon valence bonds. At that time, however, there was a report based on a space group assignment that the central C atom of pentaerythritol in the crystal was (tetragonal) pyramidal. Nitta (1926) found that the reported space group was erroneous and the C atom was actually tetrahedral. This was later verified by a full structure determination, and the tetrahedral carbon valence bonds were established. Nitta served as Vice President of IUCr from 1963 to 1969.
S. Kikuchi, a member of Nishikawa’s group, began research on electron diffraction right after the experiments by Davisson, Germer and Thomson in 1927. Kikuchi then succeeded in doing high-energy electron diffraction (HEED) studies on single crystals of mica (1928). He observed several characteristic features of HEED, now known as the Kikuchi pattern. Several crystallographers in this group, S. Miyake, R. Uyeda, N. Kato and others studied the diffraction physics of both X-rays and electrons.
In 1924 T. Ito, who studied crystallography with P. Niggli and later with W. L. Bragg, organized a research group on mineralogical crystallography at the Univ. of Tokyo. In 1933, Nitta organized a crystallographic research group at Osaka Univ.

(1945 – 1980)

Diffraction physics : N. Kato experimentally and theoretically studied X-ray dynamical diffraction, section topographs and secondary extinction. He was President of IUCr (1978~1981), and a winner of the IUCr Ewald Prize. K. Kohra was the principal crystallographer working on the construction of the Tsukuba Photon Factory, which is still one of the most productive SR sources in the world.

Mineralogical crystallography: from 1945 – 1955 T. Ito and his collaborators, R. Sadanaga, Y. Takeuchi, N. Morimoto and others, determined crystal structures of important minerals. Ito developed a powerful indexing method for X-ray powder diffraction patterns, the Ito method. During this period, Ito established the general idea of ‘cell twin’ or ‘Ito twin’ for ‘repeated twinning of unit cell level’. This twin was quite different from the macroscopic one. These results were published in X-ray Studies on Polymorphism (Maruzen, 1950).

Sadanaga and others systematized Ito’s theory of the twin space group. Takeuchi studied the crystal structures of minerals under high pressure and/or high temperature. Morimoto, M. Tokonami and Y. Koto studied structures, superstructures and phase-transitions of many minerals.

Instruments: One of the first large computers built in Japan, comparable to IBM systems, that had enough capacity for computing in crystal structure determination came into operation in 1967. A program system UNICS (universal crystallographic computing system) consisting of fundamental programs for structure determination was written by T. Sakurai, T. Ashida and others (1967), and used by many crystallographers. The first Japanese computer-controlled four-circle diffractometer was produced in 1968 by Rigaku. Then the precision as well as the speed of X-ray single crystal structure determination in Japan improved dramatically. Tsukuba photon factory 2.5GeV came into operation in 1983. It provided a large step forward for the development of crystallography in Japan which saw an ensuing growth in the number of researchers involved in structure determination.

Anomalous dispersion: Using anomalous dispersion Y. Saito and collaborators (1954) were among the first to determine absolute configuration with their work on the complex ion [Co(en)₃]³⁺. Y. Okaya, Saito and R. Pepinsky proposed the theoretically attractive Ps(u) function. Okaya and Pepinsky formulated the relationship between structure factor phases and anomalous dispersion terms. This relationship is used in the phasing method which is now most widely applied for protein crystallography.

Electron density distribution: Y. Tomiie et al. (1958) studied precise electron density distribution in diformylhydrazine and obtained a reasonable coincidence with the one calculated by the MO method. He also found the electron density of a lone pair of electrons belonging to the O atom. Saito, F. Marumo and others studied precise 3d electron distribution in some transition metal ions and compared their results with theoretical predictions. Saito, H. Iwasaki and others studied electron density distributions in charge transfer complexes.

Important compounds: Crystal structures of many important compounds, such as natural organic compounds, coordination compounds, organometallics (A. Shimada, N. Kasai and N. Yasuoka), charge transfer complexes, synthetic polymers (H. Tadokoro), oligopeptides (Ashida), etc, have been studied. Many crystallographers are engaged in research in this category, but only a few of them could be presented here for want of space.

Crystalline phase reactions : In 1977, Y. Ohashi and Y. Sasada observed that racemization occurred when crystals of an (S-α-methylbenzylamine)cobaloxime complex were exposed to X-rays. This reaction could be traced by observing changes in electron density with exposure time. Similar reactions were found in the crystals of related compounds and were extensively studied. This research exploited a new attractive research field in chemical crystallography.

Protein crystals: M. Kakudo, Ashida, N. Tanaka and others began protein crystallography in 1965, and reported a 2.3 Å resolution structure of bonito ferrocytochrome c at the IUCr meeting in 1972. Most of the MIR programs necessary were prepared by Ashida. This was the first high-resolution analysis of a protein structure in Japan. In an international collaboration involving the staff of Dorothy Hodgkin’s laboratory in England, N. Sakabe and others studied 2Zn-insulin at 3.1 Å resolution in 1972 and 1.1 Å resolution in 1984. Y. Iitaka and Y. Mitsui and others studied 2.6 Å resolution subtilisin inhibitor in 1979. Katsube’s group reported the structure of ferredoxin in 1981. From that point on protein crystallography in Japan developed rapidly in both quality and quantity.

Other biological materials: DNA, RNA and related compounds were studied by Y. Mitsui and Iitaka, Sasada’s group and K. Tomita’s group. Bacterial cilia and flagella, muscle, biomembranes, etc have been studied. Among many biophysicists who engaged in the research of these material were T. Mitsui’s group including T. Ueki, and K. Wakabayashi.

Crystallographic community

Japan joined the IUCr in 1951 with its adhering body being the National Committee for Crystallography (NCC-Japan), which adheres to the Science Council of Japan (SCJ). The Crystallographic Society of Japan (CrSJ) was organized in 1950 as the electorate for the national committee. The number of members is now about 1,300. CrSJ has held annual meetings since 1973, and has published the Journal of the Crystallographic Society of Japan (bimonthly) since 1960.

The Japanese crystallographic community has hosted several successful international meetings including the IXth Congress and General Assembly of the IUCr, Kyoto (1972), the 7^th Sagamore Conference, Nikko (1982) and the International Summer School on Crystallographic Computing, Kyoto (1983)

CrSJ and NCC-Japan jointly celebrated the 50th anniversary of crystallography in Japan in Tokyo on July 1, 2000.

Tamaichi Ashida
(ashida-t@mpd.biglobe.ne.jp)

Activities in big facilities

SPring-8

SPring-8, the largest third-generation synchrotron radiation facility in the world, provides the most powerful synchrotron radiation currently available. The Japanese Atomic Energy Research Institute (JAERI) and RIKEN (The Institute of Physical and Chemical Research) began constructing SPring-8 (Super Photon ring-8GeV) in 1991 with support from Hyogo Prefecture, universities, research institutes and industries, and opened the facility in October, 1997.

Since its completion, all aspects of its operation have been conducted by the Japan Synchrotron Radiation Research Institute (JASRI), which was designated as the sole institute for the management, operation and development of SPring-8. SPring-8 consists of a 1GeV linear accelerator and 8GeV booster synchrotron that generates an incident electron beam of 8GeV and a storage ring (electron energy, 8GeV; current, 100mA; circumference, 1436m) that holds the generated electrons. Figure 3-1-1 shows the Bird’s-eye view of SPring-8.

There are two types of light sources in SPring-8, insertion devices and bending magnets. Insertion devices are either undulators or wigglers. SPring-8 beam ports include insertion device beamlines with a 6m straight section (max. 34, existing 26), long insertion device beamlines with a 30m long straight section (max. 4, existing 1) and bending magnet beamlines (max. 24, existing 21). In-vacuum type undulators developed at SPring-8 have magnet arrays sealed in a vacuum chamber. The arrangement results in a smaller gap between arrays, allowing radiation with shorter wavelength and higher power to be generated.

There is an in-vacuum revolver variable polarization undulator, an in-vacuum figure-8 undulator, a twin helical undulator, a tandem vertical undulator, an elliptical wiggler, and others that generate a variety of polarized radiation. The characteristic photon energy of a bending magnet is 28.9 keV.

62 beamlines are available. 46 are in operation and 2 are under construction. The beamlines are classified as public beamlines, contract beamlines, JAERI/RIKEN beamlines, R&D beamlines, and beamlines for accelerator diagnosis.

Two beamlines, whose lengths are 225m, are already operational at the biomedical imaging center. Two beamlines, longer than 100m, have been developed at the RI laboratory for research on radioactive isotopes and actinide materials. A 1 km-long beamline is used for research on advanced coherent X-ray optics.

The top-up operation was started successfully at SPring-8 in May, 2004. The electron beam is injected at short intervals during user beamtime, so that the current stored in the storage ring is kept constant. The top-up operation has a number of innovative features such as (1) a perturbation-free beam injection scheme, (2) minimum injection beam loss, and (3) a high purity singlebunch beam. This “ideal top-up operation” is used by many other light source facilities around the world. The top-up operation offers the following benefits to users: (1) time averaged brilliance is increased by a factor of two, (2) improvement of thermal stability of the X-ray optics, and (3) a new filling pattern with a high bunch current that was not available in more conventional operations due to the extremely short beam life-time.

SPring-8 invites proprietary and non-proprietary research proposals in June and November and does not charge users for beam time if their research is non-proprietary. The annual operation time of Spring-8 is around 5400 hours, with more than 4200 hours available for experiments. More than 1000 research subjects are accepted annually by SPring-8, and the number of researchers involved exceeds 10000.

Hideo Ohno, SPring-8

Photon factory

The Photon Factory was the first synchrotron radiation research facility for X-rays in Japan. It operates two electron storage rings, shown in Table 1. One is a 2.5 GeV ring that has been operational since 1982. It’s emittance was 400 nm⋅rad in the beginning, but was reduced to 36 nm⋅rad with upgrades in 1986 and 1997. The other is a single bunch operated 6.5 GeV electron storage ring which had been used parasitically since 1986 and then in dedicated mode for synchrotron radiation research since 1997. This ring has a unique feature that 100 ps wide X-ray pulses are always obtained with a repeat period of 1.24 micro seconds. There are currently 7 and 4 insertion device beamlines on the 2.5 GeV and 6.5 GeV rings, respectively. The BL-2 of the 2.5 GeV ring is a soft X-ray undulator beamline which was the first in Japan and the second in the world. There are two in-vacuum undulator beamlines on the 6.5 GeV ring one of which is the first in-vacuum undulator beamline in the world and has been used extensively for the study of nuclear Bragg scattering, which makes the best use of pulsed X-Rays. A new in-vacuum X-ray undulator beamline is under construction on the 6.5 GeV ring for the study of photo-induced phase transitions in highly correlated materials.
There are 32 X-ray experimental stations out of 58 on the 2.5 GeV ring (energy ranging from 2.2 to 100 keV) and 8 X-ray experimental stations out of 9 on the 6.5 GeV rings (energy ranging from 5 to160 keV). Among those 40 X-ray stations, 22 are for non-biological diffraction/scattering experiments, 5 for protein crystal structure analysis, 2 for small angle scattering, 8 for X-ray spectroscopy, 2 for X-ray imaging and 2 for others. There are 650-700 active experimental proposals every year and approximately 2,700 users repeatedly visit the Photon Factory to carry out their experiments. Eighty to eighty-five percent of proposals are for X-ray experiments, the others are for VUV/soft X-ray experiments. Since the inauguration of the facility in 1982, a number of contributions have been made at the Photon Factory. Those are, for example, MAD analysis of protein crystal structures using synchrotron radiation data, extensive use of image plates for X-ray diffraction experiments, development and extensive use of multi-anvil cells for structure studies under high pressure and high temperature, development of an X-ray Fresnel lens, experimental studies of resonant magnetic X-ray scattering, development of a quarter wave X-ray phase plate using a Bragg-transmitted beam, use of anomalous scattering methods for the study of orbital order in crystals, the development of an in-vacuum undulator and its extensive use for the study of nuclear Bragg scattering, and extensive use of a high energy X-ray elliptical wiggler for magnetic Compton scattering.
To meet requests for more experimental opportunities on insertion device beamlines, the lattice of the 2.5 GeV ring will be modified in the summer of 2005 to increase the number of straight sections for insertion devices. The modifications place new quadrupole magnets of shorter length with higher field gradients closer to neighboring bending magnets to lengthen the existing straight sections or to create new straight sections as shown in Fig. 3-2-1. Four short straight sections of 1.5 m will be created. Furthermore, two 5 m long straight sections will lengthened to 9.2 m, and 8 other sections of 3.5 m will become more than 5 m. Except for one straight section used forelectron beam injection, a total of 13 straight sections will be available for insertion devices on the 2.5 GeV ring. Such an improvement will enable us to install longer undulators with planar or helical magnet configurations and minipole undulators with a narrower gap at the short straight sections. By adding 5 straight sections on the 6.5 GeV ring, the Photon Factory will have a total of 18 straight sections for insertion devices. An in-vacuum short period undulator beamline for structural biology is now being constructed and will be commissioned in the fall of 2005. Another in-vacuum undulator Xray beamline for materials science will be constructed and commissioned in 2006.

Tadashi Matsushita
(tadashi.matsushita@kek.jp)

Neutron facilities

Japan started atomic energy related activities well behind Western countries after World War II. In the mid 1950s the first nuclear research reactor JRR-1 (Japan Research Reactor No.1, 50kW, now preserved in a museum in Tokai) built by the Japan Atomic Energy Research Institute (JAERI) was used for neutron beam research. Neutron scattering research requiring an MW-class reactor started in the early 1960s when JAERI built the JRR-2, which could produce a thermal power of 10MW, thermal neutron flux or 2x1014 neutrons/cm2/sec. There were 9 neutron scattering instruments during its most active period. It was the first neutron source available for inelastic experiments and also played a central role in training many researchers. It was permanently shut down in 1996, as scheduled, after about 35-years of service. Side-by-side with JRR-2, the JRR-3 (10MW, 1x1014 n/cm2/sec, 6 instruments) was built with purely domestic technology for the first time. In the mid 1960s Kyoto University built its 5MW reactor named KUR (3x1013n.cm2/sec, 8 instruments; www-j.rri.kyoto-u.ac.jp/) in Kumatori. It is the only MW-class reactor owned by a university. In late 1960s and 1970s, therefore, three medium-size reactors were available for neutron scattering and other beam experiments while several high flux reactors became operational abroad such as the HFBR at Brookhaven National Laboratory (60MW, 8x1014, USA), HFIR at Oak Ridge National Laboratory (85MW, 1x1015, USA), and HFR at the Institute Laue Langevin (58MW, 3x1015, France). Japanese user’s strong demand for higher neutron flux by the early 1980s culminated in the refurbishment of the JRR-3 to double its thermal power (20MW, 3x1014) and install a new cold neutron source accompanied with a guide hall building. This refurbished reactor renamed as JRR-3M became fully operational in 1990. Currently it supports 25 neutron scattering, 2 neutron radiography and 2 prompt γ-ray analysis instruments and a total number of about 12,000 users per day (www.issp.u-tokyo.ac.jp/labs/neutron/index.html and www.jaeri.go.jp/).

Japan is one of pioneers in the field of accelerator-based neutron sources. In the mid 1960s the electron linear accelerator at Tohoku University in Sendai, dedicated to nuclear studies, was tested as an injector to a metal target to produce neutrons. It was then successfully used as a pulse neutron source for neutron diffraction experiments even after a new spallation neutron source was built at KEK (the present High Energy Accelerator Research Organization; http://kek.jp/) in Tsukuba in 1980. This neutron source, named KENS, was the first dedicated pulse neutron facility in the world and it has been operated at a proton beam power of 4kW for a total of 17 instruments and a cold source. Several more powerful sources were built abroad such as IPNS at Argonne National Laboratory (6kW, 1981, USA), LANSCE at Los Alamos National Laboratory (80kW, 1985, USA), and ISIS at Rutherford Appleton Laboratory (160kW, 1985, UK). The Japanese community demanded a much stronger pulse neutron source to follow post-KENS. KEK belonging to the Ministry of Education, Science and Culture (MONBUSHO) planned the Hadron Project consisting of four major facilities based on an intense proton accelerator (0.6MW) to be used for neutron scattering, muon science, nuclear and high energy physics. JAERI belonging to the Science and Technology Agency (STA) also planned a MWclass proton accelerator that would provide intense proton beams to two facilities for neutron scattering and R&D for nuclear transmutation. Both were very big projects costing nearly one billion US dollar each. When MONBUSHO and STA merged, it was recommended that both projects merge and be promoted jointly by JAERI and KEK. In 2001 the Japanese Government funded it for the following 6 years (later extended to a 7-year project in 2003). Fig. 3-3-1 displays a layout of the facility, now called J-PARC (Japan Proton Accelerator Research Complex; http://j-parc.jp/), which consists of 5 major facilities based on an intense proton accelerator (1MW). According to the plan, proton beams are accelerated by Linac up to 400Mev and transported into the 3GeV rapid cycling synchrotron (3GeV PS in figure) further accelerating up to 3GeV. Most of the beams are transported to the Materials and Life Science Facility (3GeV PS Experimental Area) where both neutrons and muons are produced. This neutron beam facility, tentatively called JSNS (Japan Spallation Neutron Source, 1MW), will have a total of 23 beam lines at which instruments will be installed. A small portion of the proton beams from the 3GeV PS is fed into the 50GeV synchrotron (50GeV PS) for nuclear physics and for long base-line neutrino experiments to be combined with the Super KAMIOKANDE. In the near future, a superconducting Linac will be installed at the end of the 400MeV Linac to further accelerate proton beams up to 600MeV for R&D study of nuclear transmutation.
Fig. 3-3-2 is an aerial photograph of the construction site of the J-PARC taken in February 2004, the fourth year of the 7-year project. One can see both the JRR-3M 20MW reactor-based steady source and the JSNS 1MW accelerator-based pulse source located within 800m of each other on the same campus facing the Pacific Ocean. This co-location of both neutron sources will be a great advantage for neutron science and technology and they will be available to users worldwide. The first neutron beams from JSNS are scheduled in November 2007 and a users program will start in April 2008.

The Japanese neutron community has been dominated by solid state physicists at the forefront of solid state physics and material science particularly in the field of low-dimensional magnetic and strongly-correlated electron systems including high-Tc superconductors and CMR materials. After cold neutrons became available from JRR- 3M in 1990, however, soft-matter scientists and biologists started using the domestic neutron facilities and now account for as many as one quarter of the total proposals. Another innovation in neutron crystallography is a neutron-sensitive imaging plate (IP) specially developed by the JAERI group with Fuji Film Co., which has opened up a new era of structural biology. Another important instrumental development is the wide variety of neutron optical devices such as the magnetic lens, compound prism, and supermirrors cooperatively developed by RIKEN, JAERI and KUR Groups (http://nop.riken.go.jp/indexJ.html). These devices combined with a new neutron source will lead to new instruments to reach an unexplored region of momentum-energy-spin space for promoting new fields of crystallography.

Yasuhiko Fujii, JAERI
fujii@neutrons.tokai.jaeri.go.jp

Recent developments in biological crystallography

In 1913, one year after Laue’s discovery, Nishikawa and Ono of the University of Tokyo successfully observed diffraction patterns from plant and animal fibers. Forty-six years later, M. Kakudo of IPR, founded a laboratory for protein crystallography at Osaka University. This group started to crystallize cytochrome c in 1962. After developing automatic four circle diffractometers and computing programs, they determined the structure of bonito ferrocytochrome c at 2.3 Å resolution in 1973. With the support of the Crystallographic Society of Japan, M. Kakudo and N. Yasuoka established the Research Center for Crystallography at IPR in 1978 to promote protein crystallography in Japan. In the 1970s, two additional groups were active in protein crystallography. N. Sakabe (Nagoya University) and Y. Mitsui (University of Tokyo) were working on insulin and subtilisin inhibitor protein, respectively. Another protein structure determined during the 1970s was a bacterial protease inhibitor (1977), whose structure was solved by Mitsui’s group. Many protein crystallographers were trained in these three groups. In the early 1980s two notable structures, [2Fe-2S] ferredoxin at 2.8 Å (1980) and RNase ST at 2.5 Å (1982), were reported by Kakudo’s group and by Mitsui’s group, respectively. The structures of Taka-amylase A at 3.0 Å (1980), rice ferricytochrome c at 2.0 Å (1983), cytochrome c3 at 1.8 Å (1984), a complex of subtilisin and its inhibitor protein at 2.6 Å (1984), Bowman-Birk type protease inhibitor at 3.0 Å (1986), [4Fe-4S] ferredoxin at 2.3 Å (1988), aspartate aminotransferase at 2.8 Å (1988), and omega-amino acid: pyruvate aminotransferase at 2.0 Å (1989) were determined during the 1980s.
In the 1990s, new research groups studying protein crystallography were organized by a younger generation of scientists both inside and outside of universities. The number of protein structures determined at high resolution has gradually increased. Eight membrane protein structures have been determined at high resolution using X-ray methods in Japan. In 1995, following an almost 20 year collaboration, T. Tsukihara’s group at Osaka University and S. Yoshikawa’s group at Himeji Institute of Technology succeeded in the structure determination of a bovine respiratory membrane protein complex, cytochrome c oxidase, consisting of two copies of 13 different subunits (Fig. 2-2-1). This structure, the first membrane protein structure determined from mammalian cells, was a marked breakthrough not only in crystallographic studies of membrane proteins, but also in the field of bioenergetics. Upon examination of the structures of the enzyme complex in different reaction states, these groups proposed a new theory of the proton pumping mechanism (1998, 2003). C. Toyoshima (University of Tokyo) determined the structure of the sarcoplasmic reticulum calcium pump in 2000 (Fig. 2-2-2). He successfully demonstrated the mechanism of calcium pumping by serial structural analyses of reaction intermediates (2002, 2004). T. Okada’s endeavor to crystallize a G proteincoupled receptor resulted in successful structure determination by a collaboration of SPring-8 group lead by M. Miyano and R. E. Stenkamp’s group of University of Washington in 2000. Collaborating with A. Yamaguchi (Osaka University), three young crystallographers, M. Murakami, S. Nakashima and E. Yamashita, determined the structure of the bacterial multidrug efflux transporter AcrB in 2002. The structure of rat monoamine oxidase A (2004) was the first structure of a membrane protein with an isolated single transmembrane helix. The structures of three other membrane proteins, bacteriorhodopsin by Kouyama (Nagoya University, 1999, 2004), a bacterial photoreaction center by K. Miki (Kyoto University, 2001), and photosystem II by N. Kamiya (RIKEN, 2003) have been determined. Y. Fujiyoshi (Kyoto University) has been working on the technique of cryo-electron microscopy since the 1980s. Collaborating with scientists around the world, he has determined the structures of a number of physiologically important membrane proteins and viruses, including influenza A virus (1994), a plant light-harvesting complex (1994), bacteriorhodopsin (1999), nicotinic acetylcholine receptor (1999, 2003), aquaporin 1 (2000), a voltage-sensitive sodium channel (2001), and others.
K. Namba (Osaka University) elucidated the mechanism of bacterial flagellar assembly and function by combining cryo-electron and X-ray structures (1995-2004) (Fig. 2-2-3). A. Nakagawa elucidated the structural organization of a double-shelled RNA virus based on the structure of Rice Dwarf Virus at 3.5 Å resolution (2003). Many other physiologically important protein structures have been determined in Japan since the mid 1990s. Outstanding structural studies on recombination, replication, transcription, and translation have been performed by K. Morikawa (BERI, 1999-2004) and T. Hakoshima (Nara IST, 2000), S. Yokoyama (RIKEN and University of Tokyo, 1995-2004), and I. Tanaka (Hokkaido University, 1997, 1999). After setting up a Structural Biology Center in the Photon Factory, S. Wakatsuki has made significant progress in understanding the structural biology of lysosomal protein transport (2002, 2003).
In 2002, the Japanese government started a large structural genomics program, “Protein 3000.” In addition to the highthroughput structural genomics approach led by S. Yokoyama (RIKEN), eight target oriented structural genomics projects led by I. Tanaka (Hokkaido University), S. Wakatsuki (Photon Factory), M. Tanokura (University of Tokyo), K. Miki (Kyoto University), A. Nakagawa (Osaka University), and others are included in Protein 3000.

N. Sakabe has been developing IP diffractometers at the Photon Factory since the early 1980s (Fig. 2-2-4). Before SPring-8 began operations, all protein crystallographers were dependent on him for the collection of intensity data. Many Japanese and foreign crystallographers determined a number of novel crystal structures using his detectors at the Photon Factory. The newest version, which has a high quality and high speed detector, was installed at BL-6C in the Photon Factory. S. Wakatsuki has built a new user friendly undulator beamline equipped with a CCD detector. The Photon Factory has one undulator and three bending magnet beamlines and SPring-8 has four undulator and six bending magnet beamlines for protein crystallography. Each beamline has specific features, requiring separate network systems for access. In addition to X-ray beamline facilties, the Japanese Atomic Energy Institute has a neutron beamline facility. A neutron diffractometer dedicated to protein crystals has been developed by Niimura’s group (2004).

Tomitake Tsukihara
(tsuki@protein.osaka-u.ac.jp)