1ves

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1ves, resolution 2.18Å

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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

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