4g5q

Publication Abstract from PubMed

GoLoco (GL) motif-containing proteins regulate G protein signaling by binding to Galpha subunit and acting as guanine nucleotide dissociation inhibitors. GLs of LGN are also known to bind the GDP form of Galpha(i/o) during asymmetric cell division. Here, we show that the C-terminal GL domain of LGN binds four molecules of Galpha(i).GDP. The crystal structures of Galpha(i).GDP in complex with LGN GL3 and GL4, respectively, reveal distinct GL/Galpha(i) interaction features when compared with the only high resolution structure known with GL/Galpha(i) interaction between RGS14 and Galpha(i1.) Only a few residues C-terminal to the conserved GL sequence are required for LGN GLs to bind to Galpha(i).GDP. A highly conserved "double Arg finger" sequence (RPsi(D/E)(D/E)QR) is responsible for LGN GL to bind to GDP bound to Galpha(i). Together with the sequence alignment, we suggest that the LGN GL/Galpha(i) interaction represents a general binding mode between GL motifs and Galpha(i). We also show that LGN GLs are potent guanine nucleotide dissociation inhibitors.

Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from Galphai.,Jia M, Li J, Zhu J, Wen W, Zhang M, Wang W J Biol Chem. 2012 Oct 26;287(44):36766-76. doi: 10.1074/jbc.M112.391607. Epub , 2012 Sep 5. PMID:22952234^[3]

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