1huq: Difference between revisions

Revision as of 14:05, 21 February 2008

1.8A CRYSTAL STRUCTURE OF THE MONOMERIC GTPASE RAB5C (MOUSE)

OverviewOverview

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.

About this StructureAbout this Structure

1HUQ is a Single protein structure of sequence from Mus musculus with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Structural plasticity of an invariant hydrophobic triad in the switch regions of Rab GTPases is a determinant of effector recognition., Merithew E, Hatherly S, Dumas JJ, Lawe DC, Heller-Harrison R, Lambright DG, J Biol Chem. 2001 Apr 27;276(17):13982-8. Epub 2001 Jan 25. PMID:11278565

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-[[Image:1huq.jpg|left|200px]]<br /><applet load="1huq" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1huq.jpg|left|200px]]<br /><applet load="1huq" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1huq, resolution 1.8&Aring;" />
 '''1.8A CRYSTAL STRUCTURE OF THE MONOMERIC GTPASE RAB5C (MOUSE)'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-HUQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with MG and GNP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HUQ OCA].
+HUQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GNP:'>GNP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HUQ OCA].
 ==Reference==
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 [[Category: Mus musculus]]
 [[Category: Single protein]]
-[[Category: Dumas, J.J.]]
+[[Category: Dumas, J J.]]
 [[Category: Hatherly, S.]]
 [[Category: Heller-Harrison, R.]]
-[[Category: Lambright, D.G.]]
+[[Category: Lambright, D G.]]
-[[Category: Lawe, D.C.]]
+[[Category: Lawe, D C.]]
 [[Category: Merithew, E.]]
 [[Category: GNP]]
@@ Line 27: / Line 27: @@
 [[Category: rab protein]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 16:50:10 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:05:00 2008''