38th course: structure and function of large molecular assemblies
Erice, Italy, June 8-18, 2006
The major focus of the meeting was on structure and related function for several families of biological macromolecules, with some prominence being given to viruses. The topics covered included structural investigations of small molecule interactions with proteins, multiprotein cellular assemblies, viruses and their interactions with host-cell receptors and antibodies and entire cells. A fantastic array of new protein structures solved using experimental techniques including crystallography, electron microscopy, nuclear magnetic resonance and single-molecule spectroscopic techniques were presented. State-of the-art advances in technology were highlighted, and the limitations and challenges of the individual approaches were discussed.
Notwithstanding the enormous variety of biological systems described and investigated, a number of common themes emerged. Major advances have often been the result of close interactions among structural biologists using diverse techniques and biologists, chemists, and physicists—multidisciplinary collaborations that can lead to great synergy. The “molecular machines” analogy linking the functioning of large multi-component assemblies with macroscopic machines was frequently invoked and the importance of understanding integration of the components was constantly emphasized. Beautiful computer graphics—both still and animated—of molecular and cellular processes were prevalent and left meeting participants with many vivid images of our expanding molecular atlas of living organisms.
Very exciting progress has occurred since the first Erice Meeting on Macromolecular Crystallography in 1976 when the community was small, although the meeting organizer, Michael Rossmann, claimed “We are already too many!” At that time efforts were focused on studies of proteins with great natural abundance, a few tRNAs, and several plant viruses. Three-dimensional electron micrographic reconstruction techniques were in their infancy. In the intervening 30 years, numerous advances have revolutionized the field of structural biology at all levels. Recombinant DNA technology has made it possible to clone and overexpress even naturally scarce gene products in sufficient amounts for structural investigation, and improvements in microbiological and biochemical technology have permitted scale-up for production of high quality samples for many purposes. The size of structures that can be determined has expanded by orders of magnitude, thanks to technological advances such as synchrotron radiation, high speed computers, superconducting magnets, and algorithmic developments in crystallography.
Another striking feature of the meeting was how our understanding of biology and biochemistry is constantly being related to explanations on the molecular level. Nowhere was this more apparent than with macromolecular structure and the role of conformational changes in regulating and promoting biological processes. Molecules are able to recognize each other through basic chemical interactions, but dramatic changes in molecular shapes can occur as a result of environmental factors such as pH, ionic strength, and the presence of other molecules including co-factors such as ATP, a common unit of energy currency in biology. A number of systems were described in which binding of ATP and other factors led to large conformational changes and how subsequent chemical processing such as hydrolysis of ATP can lead to regeneration of the original resting conformation. An interesting insight from these collective presentations was that the largest conformational changes are often seen to occur upon binding of a co-factor such as ATP; the energy of hydrolysis is harnessed to bias directionality, and ensure time’s arrow, rather than to cause the largest movements. Most lectures and photos can be found at http://www.crystalerice.org/erice2006/2006.htm by clicking respectively on the pointers “The Virtual Course” and “Pictures by Eddy Arnold”.
Howard Einspahr presented a copy of International Tables Volume F: Crystallography of Biological Macromolecules, as the IUCr Journals Prize to Bert Janssen (NL) for the best poster presented by a young scientist.
There were 149 scientific participants from 28 countries : eleven participants that were also at the very first Erice meeting on Crystallography of Molecular Biology received a mug with reproductions of the logo of the meeting. Amongst them, obviously, Michael Rossmann who in addition was presented with a unique ceramic plate celebrating his return as scientific Director of the event – an unexpectedly heavy workload - after 30 years.
The anonymous questionnaire filled in by participants resulted in traditional figure of merit of 3.30 (highest possible was 4) compared with a 3.25 in 2005. The average figure obtained from the question “How do you score the value of the meeting to you - from 0 to 100” was 88.8, just a bit lower than the record value 90.5 obtained in 2005.