| First Author | Jia M | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 44 | Pages | 36766-76 |
| PubMed ID | 22952234 | Mgi Jnum | J:228108 |
| Mgi Id | MGI:5705216 | Doi | 10.1074/jbc.M112.391607 |
| Citation | Jia M, et al. (2012) Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from Galphai. J Biol Chem 287(44):36766-76 |
| abstractText | 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. |
