PDBsum entry 1ndm

Immune system/hydrolase

PDB id: 1ndm

Contents

Protein chains

214 a.a. *

210 a.a. *

129 a.a. *

Waters ×598

* Residue conservation analysis

References listed in PDB file

Key reference

Title

X-Ray snapshots of the maturation of an antibody response to a protein antigen.

Authors

Y.Li, H.Li, F.Yang, S.J.Smith-Gill, R.A.Mariuzza.

Ref.

Nat Struct Biol, 2003, 10, 482-488. [DOI no: 10.1038/nsb930]

PubMed id

12740607

Abstract

The process whereby the immune system generates antibodies of higher affinities during a response to antigen (affinity maturation) is a prototypical example of molecular evolution. Earlier studies have been confined to antibodies specific for small molecules (haptens) rather than for proteins. We compare the structures of four antibodies bound to the same site on hen egg white lysozyme (HEL) at different stages of affinity maturation. These X-ray snapshots reveal that binding is enhanced, not through the formation of additional hydrogen bonds or van der Waals contacts or by an increase in total buried surface, but by burial of increasing amounts of apolar surface at the expense of polar surface, accompanied by improved shape complementarity. The increase in hydrophobic interactions results from highly correlated rearrangements in antibody residues at the interface periphery, adjacent to the central energetic hot spot. This first visualization of the maturation of antibodies to protein provides insights into the evolution of high affinity in other protein-protein interfaces.

Figure 1.
Figure 1. Electron density (stereo views) in antibody combining sites. (a) Density from the final 2F[o] - F[c] map of the H26 -HEL complex in the region of V[H]CDR2 at a resolution of 2.1 Å. (b) Density from the final 2F[o] - F[c] map of the H8 -HEL complex in the same region at a resolution of 1.9 Å. Contours are at 1 .

Figure 3.
Figure 3. Shape complementarity at antibody -HEL interfaces. (a) Molecular surface of H26 viewed at the site that interacts with HEL in the H26 -HEL complex drawn using GRASP37. Regions with higher S[c] values22, indicating closer topological match with HEL, are more blue; regions with topologically uncorrelated surfaces (S[c] = 0) are white. (b) The same view of H26 as described in a, showing the location of V[H] residues in contact with HEL. (c) Molecular surface of H8 viewed at the binding site for HEL in the H8 -HEL complex. As in a, regions with better geometric fits to the antigen are more blue. (d) The same view of H8 as described in c, showing V[H] residues that interact with HEL.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2003, 10, 482-488) copyright 2003.