2qrz
From Proteopedia
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'''Cdc42 bound to GMP-PCP: Induced Fit by Effector is Required''' | '''Cdc42 bound to GMP-PCP: Induced Fit by Effector is Required''' | ||
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| + | ==Overview== | ||
| + | GTP-binding (G) proteins regulate the flow of information in cellular signaling pathways by alternating between a GTP-bound "active" state and a GDP-bound "inactive" state. Cdc42, a member of the Rho family of Ras-related small G-proteins, plays key roles in the regulation of cell shape, motility, and growth. Here we describe the high resolution x-ray crystal structure for Cdc42 bound to the GTP analog guanylyl beta,gamma-methylene-diphosphonate (GMP-PCP) (i.e. the presumed signaling-active state) and show that it is virtually identical to the structures for the signaling-inactive, GDP-bound form of the protein, contrary to what has been reported for Ras and other G-proteins. Especially surprising was that the GMP-PCP- and GDP-bound forms of Cdc42 did not show detectable differences in their Switch I and Switch II loops. Fluorescence studies using a Cdc42 mutant in which a tryptophan residue was introduced at position 32 of Switch I also showed that there was little difference in the Switch I conformation between the GDP- and GMP-PCP-bound states (i.e. <10%), which again differed from Ras where much larger changes in Trp-32 fluorescence were observed when comparing these two nucleotide-bound states (>30%). However, the binding of an effector protein induced significant changes in the Trp-32 emission specifically from GMP-PCP-bound Cdc42, as well as in the phosphate resonances for GTP bound to this G-protein as indicated in NMR studies. An examination of the available structures for Cdc42 complexed to different effector proteins, versus the x-ray crystal structure for GMP-PCP-bound Cdc42, provides a possible explanation for how effectors can distinguish between the GTP- and GDP-bound forms of this G-protein and ensure that the necessary conformational changes for signal propagation occur. | ||
==About this Structure== | ==About this Structure== | ||
2QRZ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QRZ OCA]. | 2QRZ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QRZ OCA]. | ||
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| + | ==Reference== | ||
| + | Effector Proteins Exert an Important Influence on the Signaling-active State of the Small GTPase Cdc42., Phillips MJ, Calero G, Chan B, Ramachandran S, Cerione RA, J Biol Chem. 2008 May 16;283(20):14153-64. Epub 2008 Mar 18. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18348980 18348980] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Calero, G | + | [[Category: Calero, G.]] |
[[Category: Cerione, R A.]] | [[Category: Cerione, R A.]] | ||
[[Category: Chan, B.]] | [[Category: Chan, B.]] | ||
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[[Category: Nucleotide-binding]] | [[Category: Nucleotide-binding]] | ||
[[Category: Prenylation]] | [[Category: Prenylation]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 28 09:33:40 2008'' |
Revision as of 06:33, 28 May 2008
Cdc42 bound to GMP-PCP: Induced Fit by Effector is Required
Overview
GTP-binding (G) proteins regulate the flow of information in cellular signaling pathways by alternating between a GTP-bound "active" state and a GDP-bound "inactive" state. Cdc42, a member of the Rho family of Ras-related small G-proteins, plays key roles in the regulation of cell shape, motility, and growth. Here we describe the high resolution x-ray crystal structure for Cdc42 bound to the GTP analog guanylyl beta,gamma-methylene-diphosphonate (GMP-PCP) (i.e. the presumed signaling-active state) and show that it is virtually identical to the structures for the signaling-inactive, GDP-bound form of the protein, contrary to what has been reported for Ras and other G-proteins. Especially surprising was that the GMP-PCP- and GDP-bound forms of Cdc42 did not show detectable differences in their Switch I and Switch II loops. Fluorescence studies using a Cdc42 mutant in which a tryptophan residue was introduced at position 32 of Switch I also showed that there was little difference in the Switch I conformation between the GDP- and GMP-PCP-bound states (i.e. <10%), which again differed from Ras where much larger changes in Trp-32 fluorescence were observed when comparing these two nucleotide-bound states (>30%). However, the binding of an effector protein induced significant changes in the Trp-32 emission specifically from GMP-PCP-bound Cdc42, as well as in the phosphate resonances for GTP bound to this G-protein as indicated in NMR studies. An examination of the available structures for Cdc42 complexed to different effector proteins, versus the x-ray crystal structure for GMP-PCP-bound Cdc42, provides a possible explanation for how effectors can distinguish between the GTP- and GDP-bound forms of this G-protein and ensure that the necessary conformational changes for signal propagation occur.
About this Structure
2QRZ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Effector Proteins Exert an Important Influence on the Signaling-active State of the Small GTPase Cdc42., Phillips MJ, Calero G, Chan B, Ramachandran S, Cerione RA, J Biol Chem. 2008 May 16;283(20):14153-64. Epub 2008 Mar 18. PMID:18348980 Page seeded by OCA on Wed May 28 09:33:40 2008
