1y1a

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1y1a, resolution 2.30Å

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CRYSTAL STRUCTURE OF CALCIUM AND INTEGRIN BINDING PROTEIN

Contents

Overview

Calcium- and integrin-binding protein 1 (CIB1) is involved in the process, of platelet aggregation by binding the cytoplasmic tail of the alpha(IIb), subunit of the platelet-specific integrin alpha(Iib)beta(3). Although, poorly understood, it is widely believed that CIB1 acts as a global, signaling regulator because it is expressed in many tissues that do not, express integrin alpha(Iib)beta(3). We report the structure of human CIB1, to a resolution of 2.3 A, crystallized as a dimer. The dimer interface, includes an extensive hydrophobic patch in a crystal form with 80% solvent, content. Although the dimer form of CIB1 may not be physiologically, relevant, this intersub-unit surface is likely to be linked to alpha(IIb), binding and to the binding of other signaling partner proteins. The, C-terminal domain of CIB1 is structurally similar to other EF-hand, proteins such as calmodulin and calcineurin B. Despite structural homology, to the C-terminal domain, the N-terminal domain of CIB1 lacks, calcium-binding sites. The structure of CIB1 revealed a complex with a, molecule of glutathione in the reduced state bond to the N-terminal domain, of one of the two subunits poised to interact with the free thiol of C35., Glutathione bound in this fashion suggests CIB1 may be redox regulated., Next to the bound GSH, the orientation of residues C35, H31, and S48 is, suggestive of a cysteine-type protein phosphatase active site. The, potential enzymatic activity of CIB1 is discussed and suggests a mechanism, by which it regulates a wide variety of proteins in cells in addition to, platelets.

Disease

Known disease associated with this structure: Multiple endocrine neoplasia, type IV OMIM:[600778]

About this Structure

1Y1A is a Single protein structure of sequence from Homo sapiens with and as ligands. Known structural/functional Sites: , , and . Full crystallographic information is available from OCA.

Reference

The crystal structure of calcium- and integrin-binding protein 1: insights into redox regulated functions., Blamey CJ, Ceccarelli C, Naik UP, Bahnson BJ, Protein Sci. 2005 May;14(5):1214-21. PMID:15840829

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