Structural highlights
Function
GNAI1_HUMAN 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] [2]
Publication Abstract from PubMed
The de novo design of protein-binding peptides is challenging because it requires the identification of both a sequence and a backbone conformation favorable for binding. We used a computational strategy that iterates between structure and sequence optimization to redesign the C-terminal portion of the RGS14 GoLoco motif peptide so that it adopts a new conformation when bound to Galpha(i1). An X-ray crystal structure of the redesigned complex closely matches the computational model, with a backbone root-mean-square deviation of 1.1 A.
Computational design of the sequence and structure of a protein-binding peptide.,Sammond DW, Bosch DE, Butterfoss GL, Purbeck C, Machius M, Siderovski DP, Kuhlman B J Am Chem Soc. 2011 Mar 30;133(12):4190-2. Epub 2011 Mar 9. PMID:21388199[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cho H, Kehrl JH. Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division. J Cell Biol. 2007 Jul 16;178(2):245-55. PMID:17635935 doi:10.1083/jcb.200604114
- ↑ Johnston CA, Siderovski DP. Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2001-6. Epub 2007 Jan 30. PMID:17264214
- ↑ Sammond DW, Bosch DE, Butterfoss GL, Purbeck C, Machius M, Siderovski DP, Kuhlman B. Computational design of the sequence and structure of a protein-binding peptide. J Am Chem Soc. 2011 Mar 30;133(12):4190-2. Epub 2011 Mar 9. PMID:21388199 doi:10.1021/ja110296z
