1am4

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(New page: 200px<br /> <applet load="1am4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1am4, resolution 2.7&Aring;" /> '''COMPLEX BETWEEN CDC4...)
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[[Image:1am4.gif|left|200px]]<br /><applet load="1am4" size="350" color="white" frame="true" align="right" spinBox="true"
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<applet load="1am4" size="450" color="white" frame="true" align="right" spinBox="true"
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caption="1am4, resolution 2.7&Aring;" />
caption="1am4, resolution 2.7&Aring;" />
'''COMPLEX BETWEEN CDC42HS.GMPPNP AND P50 RHOGAP (H. SAPIENS)'''<br />
'''COMPLEX BETWEEN CDC42HS.GMPPNP AND P50 RHOGAP (H. SAPIENS)'''<br />
==Overview==
==Overview==
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Small G proteins transduce signals from plasma-membrane receptors to, control a wide range of cellular functions. These proteins are clustered, into distinct families but all act as molecular switches, active in their, GTP-bound form but inactive when GDP-bound. The Rho family of G proteins, which includes Cdc42Hs, activate effectors involved in the regulation of, cytoskeleton formation, cell proliferation and the JNK signalling pathway., G proteins generally have a low intrinsic GTPase hydrolytic activity but, there are family-specific groups of GTPase-activating proteins (GAPs) that, enhance the rate of GTP hydrolysis by up to 10(5) times. We report here, the crystal structure of Cdc42Hs, with the non-hydrolysable GTP analogue, GMPPNP, in complex with the GAP domain of p50rhoGAP at 2.7A resolution. In, the complex Cdc42Hs interacts, mainly through its switch I and II regions, with a shallow pocket on rhoGAP which is lined with conserved residues., Arg 85 of rhoGAP interacts with the P-loop of Cdc42Hs, but from, biochemical data and by analogy with the G-protein subunit G(i alpha1), we, propose that it adopts a different conformation during the catalytic cycle, which enables it to stabilize the transition state of the GTP-hydrolysis, reaction.
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Small G proteins transduce signals from plasma-membrane receptors to control a wide range of cellular functions. These proteins are clustered into distinct families but all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of G proteins, which includes Cdc42Hs, activate effectors involved in the regulation of cytoskeleton formation, cell proliferation and the JNK signalling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GTPase-activating proteins (GAPs) that enhance the rate of GTP hydrolysis by up to 10(5) times. We report here the crystal structure of Cdc42Hs, with the non-hydrolysable GTP analogue GMPPNP, in complex with the GAP domain of p50rhoGAP at 2.7A resolution. In the complex Cdc42Hs interacts, mainly through its switch I and II regions, with a shallow pocket on rhoGAP which is lined with conserved residues. Arg 85 of rhoGAP interacts with the P-loop of Cdc42Hs, but from biochemical data and by analogy with the G-protein subunit G(i alpha1), we propose that it adopts a different conformation during the catalytic cycle which enables it to stabilize the transition state of the GTP-hydrolysis reaction.
==About this Structure==
==About this Structure==
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1AM4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=1AM4 OCA].
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1AM4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=1AM4 OCA].
==Reference==
==Reference==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: Gamblin, S.J.]]
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[[Category: Gamblin, S J.]]
[[Category: Rittinger, K.]]
[[Category: Rittinger, K.]]
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[[Category: Smerdon, S.J.]]
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[[Category: Smerdon, S J.]]
[[Category: Walker, P.]]
[[Category: Walker, P.]]
[[Category: GNP]]
[[Category: GNP]]
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[[Category: gtpase activation]]
[[Category: gtpase activation]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 15:59:44 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:45:56 2008''

Revision as of 09:45, 21 February 2008


1am4, resolution 2.7Å

Drag the structure with the mouse to rotate

COMPLEX BETWEEN CDC42HS.GMPPNP AND P50 RHOGAP (H. SAPIENS)

Overview

Small G proteins transduce signals from plasma-membrane receptors to control a wide range of cellular functions. These proteins are clustered into distinct families but all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of G proteins, which includes Cdc42Hs, activate effectors involved in the regulation of cytoskeleton formation, cell proliferation and the JNK signalling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GTPase-activating proteins (GAPs) that enhance the rate of GTP hydrolysis by up to 10(5) times. We report here the crystal structure of Cdc42Hs, with the non-hydrolysable GTP analogue GMPPNP, in complex with the GAP domain of p50rhoGAP at 2.7A resolution. In the complex Cdc42Hs interacts, mainly through its switch I and II regions, with a shallow pocket on rhoGAP which is lined with conserved residues. Arg 85 of rhoGAP interacts with the P-loop of Cdc42Hs, but from biochemical data and by analogy with the G-protein subunit G(i alpha1), we propose that it adopts a different conformation during the catalytic cycle which enables it to stabilize the transition state of the GTP-hydrolysis reaction.

About this Structure

1AM4 is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP., Rittinger K, Walker PA, Eccleston JF, Nurmahomed K, Owen D, Laue E, Gamblin SJ, Smerdon SJ, Nature. 1997 Aug 14;388(6643):693-7. PMID:9262406

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