title: Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from Gαi.
abstract: GoLoco (GL) motif-containing proteins regulate G protein signaling by binding to Gα subunit and acting as guanine nucleotide dissociation inhibitors. GLs of LGN are also known to bind the GDP form of Gα(i/o) during asymmetric cell division. Here, we show that the C-terminal GL domain of LGN binds four molecules of Gα(i)·GDP. The crystal structures of Gα(i)·GDP in complex with LGN GL3 and GL4, respectively, reveal distinct GL/Gα(i) interaction features when compared with the only high resolution structure known with GL/Gα(i) interaction between RGS14 and Gα(i1.) Only a few residues C-terminal to the conserved GL sequence are required for LGN GLs to bind to Gα(i)·GDP. A highly conserved "double Arg finger" sequence (RΨ(D/E)(D/E)QR) is responsible for LGN GL to bind to GDP bound to Gα(i). Together with the sequence alignment, we suggest that the LGN GL/Gα(i) interaction represents a general binding mode between GL motifs and Gα(i). We also show that LGN GLs are potent guanine nucleotide dissociation inhibitors.
authors.affiliation: Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry and Institute of Biomedical Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.forename: Jianchao
authors.initials: J
authors.lastname: Li
authors.forename: Jinwei
authors.initials: J
authors.lastname: Zhu
authors.forename: Wenyu
authors.initials: W
authors.lastname: Wen
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhang
authors.forename: Wenning
authors.initials: W
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics; D018797:Cell Cycle Proteins; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000737:chemistry*; D006153:Guanosine Diphosphate / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D017186:Titrimetry
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C502655:LGN protein, mouse; D006153:Guanosine Diphosphate; D051960:GTP-Binding Protein alpha Subunit, Gi2