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.
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| Ligands: | , , |
| Related: | 1gfi, 1y3a, 2g83, 2hlb, 1bh2 |
| Gene: | Gnai1, Gnai-1 (Rattus norvegicus) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
