1tu3 | pdb_00001tu3
Crystal Structure of Rab5 complex with Rabaptin5 C-terminal Domain
Structural highlights
Function[RAB5A_HUMAN] Required for the fusion of plasma membranes and early endosomes. Contributes to the regulation of filopodia extension.[1] [RABE1_HUMAN] Rab effector protein acting as linker between gamma-adaptin, RAB4A and RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Stimulates RABGEF1 mediated nucleotide exchange on RAB5A.[2] [3] [4] [5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedRab5 is a small GTPase that regulates early endosome fusion. We present here the crystal structure of the Rab5 GTPase domain in complex with a GTP analog and the C-terminal domain of effector Rabaptin5. The proteins form a dyad-symmetric Rab5-Rabaptin5(2)-Rab5 ternary complex with a parallel coiled-coil Rabaptin5 homodimer in the middle. Two Rab5 molecules bind independently to the Rabaptin5 dimer using their switch and interswitch regions. The binding does not involve the Rab complementarity-determining regions. We also present the crystal structures of two distinct forms of GDP-Rab5 complexes, both of which are incompatible with Rabaptin5 binding. One has a dislocated and disordered switch I but a virtually intact switch II, whereas the other has its beta-sheet and both switch regions reorganized. Biochemical and functional analyses show that the crystallographically observed Rab5-Rabaptin5 complex also exists in solution, and disruption of this complex by mutation abrogates endosome fusion. Structural basis of Rab5-Rabaptin5 interaction in endocytosis.,Zhu G, Zhai P, Liu J, Terzyan S, Li G, Zhang XC Nat Struct Mol Biol. 2004 Oct;11(10):975-83. Epub 2004 Sep 19. PMID:15378032[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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