1fnh

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1fnh, resolution 2.8Å

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CRYSTAL STRUCTURE OF HEPARIN AND INTEGRIN BINDING SEGMENT OF HUMAN FIBRONECTIN

Contents

Overview

The crystal structure of human fibronectin (FN) type III repeats 12-14 reveals the primary heparin-binding site, a clump of positively charged residues in FN13, and a putative minor site approximately 60 A away in FN14. The IDAPS motif implicated in integrin alpha4beta1 binding is at the FN13-14 junction, rendering the critical Asp184 inaccessible to integrin. Asp184 clamps the BC loop of FN14, whose sequence (PRARI) is reminiscent of the synergy sequence (PHSRN) of FN9. Mutagenesis studies prompted by this observation reveal that both arginines of the PRARI sequence are important for alpha4beta1 binding to FN12-14. The PRARI motif may represent a new class of integrin-binding sites. The spatial organization of the binding sites suggests that heparin and integrin may bind in concert.

Disease

Known diseases associated with this structure: Ehlers-Danlos syndrome, type X, 225310 (1) OMIM:[135600]

About this Structure

1FNH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of a heparin- and integrin-binding segment of human fibronectin., Sharma A, Askari JA, Humphries MJ, Jones EY, Stuart DI, EMBO J. 1999 Mar 15;18(6):1468-79. PMID:10075919

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