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3d7m

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Revision as of 04:15, 25 December 2014

Crystal Structure of the G Protein Fast-Exchange Double Mutant I56C/Q333C

Structural highlights

3d7m is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1gfi, 1y3a, 2g83, 2hlb, 1bh2
Gene:	Gnai1, Gnai-1 (Rattus norvegicus)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[GNAI1_RAT] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

ABSTRACT. Heterotrimeric G proteins (Galphabetagamma) transmit signals from activated G protein coupled receptors (GPCRs) to downstream effectors through a guanine nucleotide signaling cycle. Numerous studies indicate that the carboxy-terminal alpha5 helix of Galpha subunits participate in Galpha-receptor binding, and previous EPR studies suggest this receptor-mediated interaction induces a rotation and translation of the alpha5 helix of the Galpha subunit [Oldham et al., Nat. Struct. Mol. Biol., 13: 772-7 (2006)]. Based on this result, an engineered disulfide bond was designed to constrain the alpha5 helix of Galphai1 into its EPR-measured receptor-associated conformation through the introduction of cysteines at positions 56 in the alpha1 helix and 333 in the alpha5 helix (I56C/Q333C Galphai1). A functional mimetic of the EPR-measured alpha5 helix dipole movement upon receptor association was additionally created by introduction of a positive charge at the amino-terminus of this helix, D328R Galphai1. Both proteins exhibit dramatically elevated basal nucleotide exchange. The 2.9 A resolution crystal structure of the I56C/Q333C Galphai1 in complex with GDP-AlF4- reveals the shift of the alpha5 helix toward the guanine nucleotide-binding site that is anticipated by EPR measurements. The structure of the I56C/Q333C Galphai1 subunit further revealed altered positions for the switch regions and throughout the Galphai1 subunit, accompanied by significantly elevated crystallographic temperature factors. Combined with previous evidence in the literature, the structural analysis supports the critical role of electrostatics of the alpha5 helix dipole and overall conformational variability during nucleotide release.

Helix dipole movement and conformational variability contribute to allosteric GDP release in Gi subunits.,Preininger A, Funk M, Meier S, Oldham W, Johnston C, Adhikary S, Kimple A, Siderovski D, Hamm H, Iverson T Biochemistry. 2009 Feb 17. PMID:19222191^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shu FJ, Ramineni S, Amyot W, Hepler JR. Selective interactions between Gi alpha1 and Gi alpha3 and the GoLoco/GPR domain of RGS14 influence its dynamic subcellular localization. Cell Signal. 2007 Jan;19(1):163-76. Epub 2006 Jul 25. PMID:16870394 doi:http://dx.doi.org/10.1016/j.cellsig.2006.06.002
↑ Preininger A, Funk M, Meier S, Oldham W, Johnston C, Adhikary S, Kimple A, Siderovski D, Hamm H, Iverson T. Helix dipole movement and conformational variability contribute to allosteric GDP release in Gi subunits. Biochemistry. 2009 Feb 17. PMID:19222191 doi:10.1021/bi801853a

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3d7m"

@@ Line 8: / Line 8: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3d7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d7m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3d7m RCSB], [http://www.ebi.ac.uk/pdbsum/3d7m PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/GNAI1_RAT GNAI1_RAT]] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:16870394</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3d7m

From Proteopedia

Revision as of 04:15, 25 December 2014

Crystal Structure of the G Protein Fast-Exchange Double Mutant I56C/Q333C

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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