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Publication Abstract from PubMed

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 Galphai 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 alpha 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/Galphai.GDP complexes. Our results also indicate that multiple and orphan GL motif proteins likely respond to G proteins with distinct mechanisms.

An Autoinhibited Conformation of LGN Reveals a Distinct Interaction Mode between GoLoco Motifs and TPR Motifs.,Pan Z, Zhu J, Shang Y, Wei Z, Jia M, Xia C, Wen W, Wang W, Zhang M Structure. 2013 Jun 4;21(6):1007-17. doi: 10.1016/j.str.2013.04.005. Epub 2013, May 9. PMID:23665171^[1]

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