Structure of guanine-nucleotide-exchange factor human Mss4 and identification of its Rab-interacting surface.

Nature
Authors
Keywords
Abstract

Guanine-nucleotide-exchange factors (GEFs) promote the exchange of GDP for GTP in Ras GTPases, and thereby positively regulate their functions. Members of the Sec4/Ypt1/Rab branch of the Ras superfamily are essential for vesicular transport. A GEF for a subset of Rab proteins, termed mammalian suppressor of Sec4 (Mss4), has been identified. Here we use multidimensional NMR to determine the structure of human Mss4 (hMss4), which is the first tertiary structure established for a protein with GEF activity. Mss4 contains a central beta-sheet sandwiched between two small sheets. It also binds a Zn2+ ion through Cys 23, Cys 26, Cys 94 and Cys 97. The Rab-binding surface of hMss4 has subsequently been delineated using chemical-shift perturbation experiments and site-directed mutagenesis. The active site of hMss4 involves the Zn(2+)-binding region and a neighbouring loop.

Year of Publication
1995
Journal
Nature
Volume
376
Issue
6543
Pages
788-91
Date Published
1995 Aug 31
ISSN
0028-0836
DOI
10.1038/376788a0
PubMed ID
7651540
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