5js8 | pdb_00005js8
Structural Model of a Protein alpha subunit in complex with GDP obtained with SAXS and NMR residual couplings
Structural highlights
FunctionGNAI1_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 PubMedHeterotrimeric G proteins play a pivotal role in the signal-transduction pathways initiated by G-protein-coupled receptor (GPCR) activation. Agonist-receptor binding causes GDP-to-GTP exchange and dissociation of the Galpha subunit from the heterotrimeric G protein, leading to downstream signaling. Here, we studied the internal mobility of a G-protein alpha subunit in its apo and nucleotide-bound forms and characterized their dynamical features at multiple time scales using solution NMR, small-angle X-ray scattering, and molecular dynamics simulations. We find that binding of GTP analogs leads to a rigid and closed arrangement of the Galpha subdomain, whereas the apo and GDP-bound forms are considerably more open and dynamic. Furthermore, we were able to detect two conformational states of the Galpha Ras domain in slow exchange whose populations are regulated by binding to nucleotides and a GPCR. One of these conformational states, the open state, binds to the GPCR; the second conformation, the closed state, shows no interaction with the receptor. Binding to the GPCR stabilizes the open state. This study provides an in-depth analysis of the conformational landscape and the switching function of a G-protein alpha subunit and the influence of a GPCR in that landscape. Conformational dynamics of a G-protein alpha subunit is tightly regulated by nucleotide binding.,Goricanec D, Stehle R, Egloff P, Grigoriu S, Pluckthun A, Wagner G, Hagn F Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):E3629-38. doi:, 10.1073/pnas.1604125113. Epub 2016 Jun 13. PMID:27298341[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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