2g77
From Proteopedia
(New page: 200px<br /><applet load="2g77" size="450" color="white" frame="true" align="right" spinBox="true" caption="2g77, resolution 2.26Å" /> '''Crystal Structure of...) |
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| - | [[Image:2g77.gif|left|200px]]<br /><applet load="2g77" size=" | + | [[Image:2g77.gif|left|200px]]<br /><applet load="2g77" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2g77, resolution 2.26Å" /> | caption="2g77, resolution 2.26Å" /> | ||
'''Crystal Structure of Gyp1 TBC domain in complex with Rab33 GTPase bound to GDP and AlF3'''<br /> | '''Crystal Structure of Gyp1 TBC domain in complex with Rab33 GTPase bound to GDP and AlF3'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Rab GTPases regulate membrane trafficking by cycling between inactive | + | Rab GTPases regulate membrane trafficking by cycling between inactive (GDP-bound) and active (GTP-bound) conformations. The duration of the active state is limited by GTPase-activating proteins (GAPs), which accelerate the slow intrinsic rate of GTP hydrolysis. Proteins containing TBC (Tre-2, Bub2 and Cdc16) domains are broadly conserved in eukaryotic organisms and function as GAPs for Rab GTPases as well as GTPases that control cytokinesis. An exposed arginine residue is a critical determinant of GAP activity in vitro and in vivo. It has been expected that the catalytic mechanism of TBC domains would parallel that of Ras and Rho family GAPs. Here we report crystallographic, mutational and functional analyses of complexes between Rab GTPases and the TBC domain of Gyp1p. In the crystal structure of a TBC-domain-Rab-GTPase-aluminium fluoride complex, which approximates the transition-state intermediate for GTP hydrolysis, the TBC domain supplies two catalytic residues in trans, an arginine finger analogous to Ras/Rho family GAPs and a glutamine finger that substitutes for the glutamine in the DxxGQ motif of the GTPase. The glutamine from the Rab GTPase does not stabilize the transition state as expected but instead interacts with the TBC domain. Strong conservation of both catalytic fingers indicates that most TBC-domain GAPs may accelerate GTP hydrolysis by a similar dual-finger mechanism. |
==About this Structure== | ==About this Structure== | ||
| - | 2G77 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with MG, GDP and AF3 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2G77 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=GDP:'>GDP</scene> and <scene name='pdbligand=AF3:'>AF3</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G77 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Eathiraj, S.]] | [[Category: Eathiraj, S.]] | ||
| - | [[Category: Lambright, D | + | [[Category: Lambright, D G.]] |
[[Category: Munson, M.]] | [[Category: Munson, M.]] | ||
[[Category: Pan, X.]] | [[Category: Pan, X.]] | ||
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[[Category: vesicular trafficking]] | [[Category: vesicular trafficking]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:28:51 2008'' |
Revision as of 15:28, 21 February 2008
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Crystal Structure of Gyp1 TBC domain in complex with Rab33 GTPase bound to GDP and AlF3
Overview
Rab GTPases regulate membrane trafficking by cycling between inactive (GDP-bound) and active (GTP-bound) conformations. The duration of the active state is limited by GTPase-activating proteins (GAPs), which accelerate the slow intrinsic rate of GTP hydrolysis. Proteins containing TBC (Tre-2, Bub2 and Cdc16) domains are broadly conserved in eukaryotic organisms and function as GAPs for Rab GTPases as well as GTPases that control cytokinesis. An exposed arginine residue is a critical determinant of GAP activity in vitro and in vivo. It has been expected that the catalytic mechanism of TBC domains would parallel that of Ras and Rho family GAPs. Here we report crystallographic, mutational and functional analyses of complexes between Rab GTPases and the TBC domain of Gyp1p. In the crystal structure of a TBC-domain-Rab-GTPase-aluminium fluoride complex, which approximates the transition-state intermediate for GTP hydrolysis, the TBC domain supplies two catalytic residues in trans, an arginine finger analogous to Ras/Rho family GAPs and a glutamine finger that substitutes for the glutamine in the DxxGQ motif of the GTPase. The glutamine from the Rab GTPase does not stabilize the transition state as expected but instead interacts with the TBC domain. Strong conservation of both catalytic fingers indicates that most TBC-domain GAPs may accelerate GTP hydrolysis by a similar dual-finger mechanism.
About this Structure
2G77 is a Protein complex structure of sequences from Mus musculus and Saccharomyces cerevisiae with , and as ligands. Full crystallographic information is available from OCA.
Reference
TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism., Pan X, Eathiraj S, Munson M, Lambright DG, Nature. 2006 Jul 20;442(7100):303-6. PMID:16855591
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