Structure, exchange determinants, and family-wide rab specificity of the tandem helical bundle and Vps9 domains of Rabex-5
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
Cell. 2004 Sep 3;118(5):607-17. Link to article on publisher's site
Delprato, Anna M.; Merithew, Eric Lee; and Lambright, David G., "Structure, exchange determinants, and family-wide rab specificity of the tandem helical bundle and Vps9 domains of Rabex-5" (2004). GSBS Student Publications. 267.