1hxr
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(New page: 200px<br /><applet load="1hxr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hxr, resolution 1.65Å" /> '''CRYSTAL STRUCTURE OF...)
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Revision as of 14:46, 20 November 2007
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CRYSTAL STRUCTURE OF MSS4 AT 1.65 ANGSTROMS
Overview
Monomeric Rab GTPases function as ubiquitous regulators of intracellular, membrane trafficking. Mss4, an evolutionarily conserved Rab accessory, factor, promotes nucleotide release from exocytic but not endocytic Rab, GTPases. Here we describe the results of a high-resolution, crystallographic and mutational analysis of Mss4. The 1.65 A crystal, structure of Mss4 reveals a network of direct and water-mediated, interactions that stabilize a partially exposed structural subdomain, derived from four highly conserved but nonconsecutive sequence elements., The conserved subdomain contains the invariant cysteine residues required, for Zn2+ binding as well as the residues implicated in the interaction, with Rab GTPases. A strictly conserved DPhiPhi motif, consisting of an, invariant aspartic acid residue (Asp 73) followed by two bulky hydrophobic, residues (Met 74 and Phe 75), encodes a prominently exposed 3(10) helical, turn in which the backbone is well-ordered but the side chains of the, conserved residues are highly exposed and do not engage in intramolecular, interactions. Substitution of any of these residues with alanine, dramatically impairs nucleotide release activity toward Rab3A, indicating, that the DPhiPhi motif is a critical element of the Rab interaction, epitope. In particular, mutation of Phe 75 results in a defect as severe, as that observed for mutation of Asp 96, which is located near the zinc, binding site at the opposite end of the conserved subdomain. Despite, severe defects, however, none of the mutant proteins is catalytically, dead. Taken together, the results suggest a concerted mechanism in which, distal elements of the conserved Rab interaction epitope cooperatively, facilitate nucleotide release.
About this Structure
1HXR is a Single protein structure of sequence from Rattus norvegicus with ZN as ligand. Full crystallographic information is available from OCA.
Reference
A helical turn motif in Mss4 is a critical determinant of Rab binding and nucleotide release., Zhu Z, Dumas JJ, Lietzke SE, Lambright DG, Biochemistry. 2001 Mar 13;40(10):3027-36. PMID:11258916
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