1bh2: Difference between revisions
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'''A326S MUTANT OF AN INHIBITORY ALPHA SUBUNIT''' | {{Structure | ||
|PDB= 1bh2 |SIZE=350|CAPTION= <scene name='initialview01'>1bh2</scene>, resolution 2.1Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=GSP:5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE'>GSP</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''A326S MUTANT OF AN INHIBITORY ALPHA SUBUNIT''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1BH2 is a [ | 1BH2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BH2 OCA]. | ||
==Reference== | ==Reference== | ||
The A326S mutant of Gialpha1 as an approximation of the receptor-bound state., Posner BA, Mixon MB, Wall MA, Sprang SR, Gilman AG, J Biol Chem. 1998 Aug 21;273(34):21752-8. PMID:[http:// | The A326S mutant of Gialpha1 as an approximation of the receptor-bound state., Posner BA, Mixon MB, Wall MA, Sprang SR, Gilman AG, J Biol Chem. 1998 Aug 21;273(34):21752-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9705312 9705312] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: signal transduction protein]] | [[Category: signal transduction protein]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:10:57 2008'' | ||
Revision as of 11:10, 20 March 2008
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
A326S MUTANT OF AN INHIBITORY ALPHA SUBUNIT
OverviewOverview
Agonist-bound heptahelical receptors activate heterotrimeric G proteins by catalyzing exchange of GDP for GTP on their alpha subunits. In search of an approximation of the receptor-alpha subunit complex, we have considered the properties of A326S Gialpha1, a mutation discovered originally in Gsalpha (Iiri, T., Herzmark, P., Nakamoto, J. M., Van Dop, C., and Bourne, H. R. (1994) Nature 371, 164-168) that mimics the effect of receptor on nucleotide exchange. The mutation accelerates dissociation of GDP from the alphai1beta1gamma2 heterotrimer by 250-fold. Nevertheless, affinity of mutant Gialpha1 for GTPgammaS is high in the presence of Mg2+, and the mutation has no effect on the intrinsic GTPase activity of the alpha subunit. The mutation also uncouples two activities of betagamma: stabilization of the GDP-bound alpha subunit (which is retained) and retardation of GDP dissociation from the heterotrimer (which is lost). For wild-type and mutant Gialpha1, beta gamma prevents irreversible inactivation of the alpha subunit at 30 degreesC. However, the mutation accelerates irreversible inactivation of alpha at 37 degreesC despite the presence of beta gamma. Structurally, the mutation weakens affinity for GTPgammaS by steric crowding: a 2-fold increase in the number of close contacts between the protein and the purine ring of the nucleotide. By contrast, we observe no differences in structure at the GDP binding site between wild-type heterotrimers and those containing A326S Gialpha1. However, the GDP binding site is only partially occupied in crystals of G protein heterotrimers containing A326S Gialpha1. In contrast to original speculations about the structural correlates of receptor-catalyzed nucleotide exchange, rapid dissociation of GDP can be observed in the absence of substantial structural alteration of a Galpha subunit in the GDP-bound state.
About this StructureAbout this Structure
1BH2 is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
ReferenceReference
The A326S mutant of Gialpha1 as an approximation of the receptor-bound state., Posner BA, Mixon MB, Wall MA, Sprang SR, Gilman AG, J Biol Chem. 1998 Aug 21;273(34):21752-8. PMID:9705312
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