An autoinhibited conformation of LGN reveals a distinct interaction mode between GoLoco motifs and TPR motifs.
An autoinhibited conformation of LGN reveals a distinct interaction mode between GoLoco motifs and TPR motifs.
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DOI：
10.1016/j.str.2013.04.005
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发表时间：
2013-06
期刊：
影响因子：
5.7
通讯作者：
Z. Pan;Jinwei Zhu;Y. Shang;Zhiyi Wei;M. Jia;C. Xia;W. Wen;Wenning Wang;Mingjie Zhang
中科院分区：
文献类型：
--
作者：
Z. Pan;Jinwei Zhu;Y. Shang;Zhiyi Wei;M. Jia;C. Xia;W. Wen;Wenning Wang;Mingjie Zhang
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 Gαito 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/Gαi·GDP complexes. Our results also indicate that multiple and orphan GL motif proteins likely respond to G proteins with distinct mechanisms.
