Crystal structure of Bence Jones protein rhe (3 A) and its unique domain-domain association.

Published on Apr 1, 1979in Journal of Molecular Biology5.067
· DOI :10.1016/0022-2836(79)90475-3
Bi-Cheng Wang48
Estimated H-index: 48
(University of Pittsburgh),
C. S. Yoo8
Estimated H-index: 8
(University of Pittsburgh),
Martin Sax21
Estimated H-index: 21
(University of Pittsburgh)
Abstract The crystal structure of protein Rhe, a lambda type V L dimer, has been determined at a resolution of 3 A by the method of multiple isomorphous replacement supplemented with anomalous scattering data. A crystallographic sequence was assigned from an interpretation of the electron density map in an optical comparator and is compared with a chemically determined partial amino acid sequence. The monomeric unit of Rhe, as determined crystallographically, contains 113 amino acids, 110 belonging to the variable region and three belonging to the constant segment of a light chain. The single polypeptide chain constituting the monomer forms a nine-stranded β-barrel characteristic of V domains. The β-pleated sheet surrounds an ellipsoidally shaped interior core of approximately 10 A × 15 A × 25 A in size. The monomers that are related by the crystallographic dyad are held together as dimers by interdomain hydrogen bonds and hydrophobic interactions. At one end of the dimer is an opening which is lined exclusively by residues from the hypervariable regions. A comparison of Rhe with Rei, a kappa type V L dimer (Epp et al. , 1975), revealed that monomers of Rhe and Rei dimerized differently. Their respective dyad and pseudodyad of dimerization are not the same, and this causes a variation in the overall steric arrangement of the hypervariable regions in the two cavities. In adition a dissimilarity was observed in the non-hypervariable segment linking the first and second hypervariable regions. This segment is in the form of a loop and it includes most of the residues participating in the interdomain interactions stabilizing dimer formation in both proteins and these loop positions differ by as much as 7 A. Our results also show that there is a good correlation between the dissimilarity of the loop position and the difference in the domain-association. Our preliminary analysis indicates that the positions of the corresponding non-hypervariable loops in V domains may be determined in part by the residues in the hypervariable regions. Accordingly, the three-dimensional structure of Rhe suggests that this nonhypervariable loop in V L and its counterpart in V H may have an important biological function in antibody specificity and variability by virtue of their influence over the architecture of the complementarity site.
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