title: An autoinhibited conformation of LGN reveals a distinct interaction mode between GoLoco motifs and TPR motifs.
abstract: LGN plays essential roles in asymmetric cell divisions via its N-terminal TPR-motif-mediated binding to mInsc and NuMA. This scaffolding activity requires the release of the autoinhibited conformation of LGN by binding of Gα(i) to its C-terminal GoLoco (GL) motifs. The interaction between the GL and TPR motifs of LGN represents a distinct GL/target binding mode with an unknown mechanism. Here, we show that two consecutive GL motifs of LGN form a minimal TPR-motif-binding unit. GL12 and GL34 bind to TPR0-3 and TPR4-7, respectively. The crystal structure of a truncated LGN reveals that GL34 forms a pair of parallel α helices and binds to the concave surface of TPR4-7, thereby preventing LGN from binding to other targets. Importantly, the GLs bind to TPR motifs with a mode distinct from that observed in the GL/Gα(i)·GDP complexes. Our results also indicate that multiple and orphan GL motif proteins likely respond to G proteins with distinct mechanisms.
authors.affiliation: Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Pan
authors.forename: Jinwei
authors.initials: J
authors.lastname: Zhu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shang
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Wei
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.forename: Caihao
authors.initials: C
authors.lastname: Xia
authors.forename: Wenyu
authors.initials: W
authors.lastname: Wen
authors.forename: Wenning
authors.initials: W
authors.lastname: Wang
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhang
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: C102754:GPSM2 protein, human; D047908:Intracellular Signaling Peptides and Proteins