4g5s | pdb_00004g5s
Structure of LGN GL3/Galphai3 complex
Structural highlights
DiseaseGNAI3_HUMAN Defects in GNAI3 are the cause of auriculocondylar syndrome 1 (ARCND1) [MIM:602483. ARCND1 is an autosomal dominant craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia.[1] FunctionGNAI3_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. G(k) is the stimulatory G protein of receptor-regulated K(+) channels. The active GTP-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.[2] Publication Abstract from PubMedGoLoco (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. References
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