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| {{STRUCTURE_1huq| PDB=1huq | SCENE= }} | | {{STRUCTURE_1huq| PDB=1huq | SCENE= }} |
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| '''1.8A CRYSTAL STRUCTURE OF THE MONOMERIC GTPASE RAB5C (MOUSE)'''
| | ===1.8A CRYSTAL STRUCTURE OF THE MONOMERIC GTPASE RAB5C (MOUSE)=== |
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| ==Overview==
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| Rab GTPases function as regulatory components of an evolutionarily conserved machinery that mediates docking, priming, and fusion of vesicles with intracellular membranes. We have previously shown that the active conformation of Rab3A is stabilized by a substantial hydrophobic interface between the putative conformational switch regions (Dumas, J. J., Zhu, Z., Connolly, J. L., and Lambright, D. G. (1999) Structure 7, 413-423). A triad of invariant hydrophobic residues at this switch interface (Phe-59, Trp-76, and Tyr-91) represents a major interaction determinant between the switch regions of Rab3A and the Rab3A-specific effector Rabphilin3A (Ostermeier, C., and Brunger, A. T. (1999) Cell 96, 363-374). Here, we report the crystal structure of the active form of Rab5C, a prototypical endocytic Rab GTPase. As is true for Rab3A, the active conformation of Rab5C is stabilized by a hydrophobic interface between the switch regions. However, the conformation of the invariant hydrophobic triad (residues Phe-58, Trp-75, and Tyr-90 in Rab5C) is dramatically altered such that the resulting surface is noncomplementary to the switch interaction epitope of Rabphilin3A. This structural rearrangement reflects a set of nonconservative substitutions in the hydrophobic core between the central beta sheet and the alpha2 helix. These observations demonstrate that structural plasticity involving an invariant hydrophobic triad at the switch interface contributes to the mechanism by which effectors recognize distinct Rab subfamilies. Thus, the active conformation of the switch regions conveys information about the identity of a particular Rab GTPase as well as the state of the bound nucleotide.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11278565}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11278565 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11278565}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Membrane trafficking]] | | [[Category: Membrane trafficking]] |
| [[Category: Rab protein]] | | [[Category: Rab protein]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:14:57 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 08:44:31 2008'' |