STRUCTURE OF THE VARIABLE DOMAIN OF HUMAN IMMUNOGLOBULIN [[kappa]]_IV LIGHT CHAIN LEN. D.-B. Huang, C. Ainsworth, C.-H. Chang, F. J. Stevens, M. Schiffer, Center for Mechanistic Biology and Biotechnology, Argonne National Laboratory, Argonne, IL 60439-4833

The structure of [[kappa]]_IV protein LEN was determined using molecular replacement with the [[kappa]]_[[Iota]] protein REI as a search structure. The R factor is 15% for data extending to 1.8 Å. The protein was crystallized from 1.5 M ammonium sulfate in space group C222₁: the unit cell dimensions are a=43.1, b=83.5, and c=54;5 Å. There is one V domain in the asymmetric unit. The crystallographic twofold axis parallel to the b axis forms the twofold of the dimer observed in other crystal structures of light chains. Although the geometry of this dimer is similar to that observed in human [[kappa]]_[[Iota]] type protein REI and mouse protein McPC603, the crystal contacts are different. The LEN dimers form a very tightly packed crystal, with head to tail contacts. All other kappa V domain dimers form a helix related by the sixfold screw axis of the unit cell; the contacts between neighboring dimers are through residues 9-12 forming a [[beta]]-pleated sheet utilizing a local or crystallographic twofold axis. We speculate that this contact in the LEN crystal is not energetically favorable, since Ser residues 9 and 12 are replaced by Asp and Ala, respectively. Protein LEN has six additional residues in its CDR1 segment compared with REI. The LEN CDR1 segment has the same length as murine [[kappa]] light chain McPC603; its amino acid sequence differs in 5 out of 17 residues. The conformations of these segments are also homologous. Proteins with closely related sequences to LEN form various deposits in patients, while LEN does not; therefore it can serve as a standard to identify pathogenic features of light chains.

This work was supported by the U.S. Department of Energy, Office of Health and Environmental Research, under Contract No. W-31-109-ENG38 and by U. S. Public Health Service Grant DK43757.