3mjh | pdb_00003mjh
Crystal Structure of Human Rab5A in complex with the C2H2 Zinc Finger of EEA1
Structural highlights
FunctionRAB5A_HUMAN Required for the fusion of plasma membranes and early endosomes. Contributes to the regulation of filopodia extension.[1] 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 PubMedRegulation of endosomal trafficking by Rab GTPases depends on selective interactions with multivalent effectors, including EEA1 and Rabenosyn-5, which facilitate endosome tethering, sorting, and fusion. Both EEA1 and Rabenosyn-5 contain a distinctive N-terminal C(2)H(2) zinc finger that binds Rab5. How these C(2)H(2) zinc fingers recognize Rab GTPases remains unknown. Here, we report the crystal structure of Rab5A in complex with the EEA1 C(2)H(2) zinc finger. The binding interface involves all elements of the zinc finger as well as a short N-terminal extension but is restricted to the switch and interswitch regions of Rab5. High selectivity for Rab5 and, to a lesser extent Rab22, is observed in quantitative profiles of binding to Rab family GTPases. Although critical determinants are identified in both switch regions, Rab4-to-Rab5 conversion-of-specificity mutants reveal an essential requirement for additional substitutions in the proximal protein core that are predicted to indirectly influence recognition through affects on the structure and conformational stability of the switch regions. Structural basis for Rab GTPase recognition and endosome tethering by the C2H2 zinc finger of Early Endosomal Autoantigen 1 (EEA1).,Mishra A, Eathiraj S, Corvera S, Lambright DG Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10866-71. Epub 2010 Jun 1. PMID:20534488[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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