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2ot3

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2ot3, resolution 2.10Å ()
Gene: RABGEF1, RABEX5 (Homo sapiens), RAB21, KIAA0118 (Homo sapiens)
Domains: VPS9, Rab21
Related: 1txu, 1z0i
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Crystal structure of rabex-5 VPS9 domain in complex with nucleotide free RAB21

Publication Abstract from PubMed

RABEX-5 and other exchange factors with VPS9 domains regulate endocytic trafficking through activation of the Rab family GTPases RAB5, RAB21 and RAB22. Here we report the crystal structure of the RABEX-5 catalytic core in complex with nucleotide-free RAB21, a key intermediate in the exchange reaction pathway. The structure reveals how VPS9 domain exchange factors recognize Rab GTPase substrates, accelerate GDP release and stabilize the nucleotide-free conformation. We further identify an autoinhibitory element in a predicted amphipathic helix located near the C terminus of the VPS9 domain. The autoinhibitory element overlaps with the binding site for the multivalent effector RABAPTIN-5 and potently suppresses the exchange activity of RABEX-5. Autoinhibition can be partially reversed by mutation of conserved residues on the nonpolar face of the predicted amphipathic helix or by assembly of the complex with RABAPTIN-5.

Structural basis for Rab GTPase activation by VPS9 domain exchange factors., Delprato A, Lambright DG, Nat Struct Mol Biol. 2007 May;14(5):406-12. Epub 2007 Apr 22. PMID:17450153

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2OT3 is a 2 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Delprato A, Lambright DG. Structural basis for Rab GTPase activation by VPS9 domain exchange factors. Nat Struct Mol Biol. 2007 May;14(5):406-12. Epub 2007 Apr 22. PMID:17450153 doi:10.1038/nsmb1232

Page seeded by OCA on Tue Feb 17 14:54:16 2009

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