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1z96

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Revision as of 05:11, 21 November 2007 by OCA (Talk | contribs)
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1z96, resolution 1.80Å

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Crystal structure of the Mud1 UBA domain

Overview

The ubiquitin-pathway associated (UBA) domain is a 40-residue, polyubiquitin-binding motif. The Schizosaccharomyces pombe protein Mud1 is, an ortholog of the Saccharomyces cerevisiae DNA-damage response protein, Ddi1 and binds to K48-linked polyubiquitin through its UBA domain. We have, solved the crystal structure of Mud1 UBA at 1.8 angstroms resolution, revealing a canonical three-helical UBA fold. We have probed the, interactions of this domain using mutagenesis, surface plasmon resonance, NMR and analytical ultracentrifugation. We show that the ubiquitin-binding, surface of Mud1 UBA extends beyond previously recognized motifs and can be, functionally dissected into primary and secondary ubiquitin-binding sites., Mutation of Phe330 to alanine, a residue exposed between helices 2 and 3, significantly reduces the affinity of the Mud1 UBA domain for K48-linked, polyubiquitin, despite leaving the primary binding surface functionally, intact. Moreover, K48-linked diubiquitin binds a single Mud1 UBA domain, even in the presence of excess UBA. We therefore propose a mechanism for, the recognition of K48-linked polyubiquitin chains by Mud1 in which, diubiquitin units are specifically recognized by a single UBA domain.

About this Structure

1Z96 is a Single protein structure of sequence from Schizosaccharomyces pombe. Full crystallographic information is available from OCA.

Reference

Mechanism of Lys48-linked polyubiquitin chain recognition by the Mud1 UBA domain., Trempe JF, Brown NR, Lowe ED, Gordon C, Campbell ID, Noble ME, Endicott JA, EMBO J. 2005 Sep 21;24(18):3178-89. Epub 2005 Sep 1. PMID:16138082

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