1ves

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Template:STRUCTURE 1ves

Structure of New Antigen Receptor variable domain from sharks


Overview

The Ig new antigen receptors (IgNARs) are single-domain antibodies found in the serum of sharks. Here, we report 2.2- and 2.8-A structures of the type 2 IgNAR variable domains 12Y-1 and 12Y-2. Structural features include, first, an Ig superfamily topology transitional between cell adhesion molecules, antibodies, and T cell receptors; and, second, a vestigial complementarity-determining region 2 at the "bottom" of the molecule, apparently discontinuous from the antigen-binding paratope and similar to that observed in cell adhesion molecules. Thus, we suggest that IgNARs originated as cell-surface adhesion molecules coopted to the immune repertoire and represent an evolutionary lineage independent of variable heavy chain/variable light chain type antibodies. Additionally, both 12Y-1 and 12Y-2 form unique crystallographic dimers, predominantly mediated by main-chain framework interactions, which represent a possible model for primordial cell-based interactions. Unusually, the 12Y-2 complementarity-determining region 3 also adopts an extended beta-hairpin structure, suggesting a distinct selective advantage in accessing cryptic antigenic epitopes.

About this Structure

1VES is a Single protein structure of sequence from Orectolobus maculatus. Full crystallographic information is available from OCA.

Reference

Structural evidence for evolution of shark Ig new antigen receptor variable domain antibodies from a cell-surface receptor., Streltsov VA, Varghese JN, Carmichael JA, Irving RA, Hudson PJ, Nuttall SD, Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12444-9. Epub 2004 Aug 10. PMID:15304650 Page seeded by OCA on Sat May 3 12:27:30 2008

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