Structure, exchange determinants, and family-wide rab specificity of the tandem helical bundle and Vps9 domains of Rabex-5
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UMass Chan Affiliations
Program in Molecular Medicine and Department of Biochemistry and Molecular PharmacologyGraduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2004-09-02Keywords
Amino Acid Sequence; Animals; Carrier Proteins; Catalytic Domain; Endocytosis; Guanine Nucleotide Exchange Factors; Humans; *Intracellular Signaling Peptides and Proteins; Models, Molecular; Molecular Sequence Data; Mutation; Phenylalanine; Protein Binding; Protein Structure, Secondary; Sequence Homology, Amino Acid; rab GTP-Binding Proteins; rab5 GTP-Binding ProteinsLife Sciences
Medicine and Health Sciences
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The Rab5 GTPase, an essential regulator of endocytosis and endosome biogenesis, is activated by guanine-nucleotide exchange factors (GEFs) that contain a Vps9 domain. Here, we show that the catalytic core of the Rab GEF Rabex-5 has a tandem architecture consisting of a Vps9 domain stabilized by an indispensable helical bundle. A family-wide analysis of Rab specificity demonstrates high selectivity for Rab5 subfamily GTPases. Conserved exchange determinants map to a common surface of the Vps9 domain, which recognizes invariant aromatic residues in the switch regions of Rab GTPases and selects for the Rab5 subfamily by requiring a small nonacidic residue preceding a critical phenylalanine in the switch I region. These and other observations reveal unexpected similarity with the Arf exchange site in the Sec7 domain.Source
Cell. 2004 Sep 3;118(5):607-17. Link to article on publisher's siteDOI
10.1016/j.cell.2004.08.009Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33597PubMed ID
15339665Related Resources
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