Dissecting the structural basis of MEIG1 interaction with PACRG.
Dissecting the structural basis of MEIG1 interaction with PACRG.
复制标题
剖析 MEIG1 与 PACRG 相互作用的结构基础
DOI：
10.1038/srep18278
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发表时间：
2016-01-04
影响因子：
4.6
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Li W;Walavalkar NM;Buchwald WA;Teves ME;Zhang L;Liu H;Bilinovich S;Peterson DL;Strauss JF 3rd;Williams DC Jr;Zhang Z
减数分裂表达基因 1 (MEIG1) 的产物存在于精母细胞的细胞体中，并通过帕金共调控基因 (PACRG) 募集到 manchette（一种延长精子细胞特有的结构）。该复合物对于在精子鞭毛组装过程中将货物定位到 manchette 至关重要。在这里，我们展示了 MEIG1 采用独特的折叠，为与其他蛋白质相互作用提供了大的表面。我们对 12 个暴露和保守的氨基酸进行了突变，结果表明其中四个突变（W50A、K57E、F66A、Y68A）显着减少了与 PACRG 的结合。这四种氨基酸在蛋白质的一端形成连续的疏水斑。此外，这四种突变中的每一种都会削弱 MEIG1 在细菌中表达时稳定 PACRG 的能力。这些研究共同确定了 MEIG1 的独特结构和关键相互作用表面，并提供了一个框架来探索 MEIG1 如何招募蛋白质来构建精子尾部。
The product of the meiosis-expressed gene 1 (MEIG1) is found in the cell bodies of spermatocytes and recruited to the manchette, a structure unique to elongating spermatids, by Parkin co-regulated gene (PACRG). This complex is essential for targeting cargo to the manchette during sperm flagellum assembly. Here we show that MEIG1 adopts a unique fold that provides a large surface for interacting with other proteins. We mutated 12 exposed and conserved amino acids and show that four of these mutations (W50A, K57E, F66A, Y68A) dramatically reduce binding to PACRG. These four amino acids form a contiguous hydrophobic patch on one end of the protein. Furthermore, each of these four mutations diminishes the ability of MEIG1 to stabilize PACRG when expressed in bacteria. Together these studies establish the unique structure and key interaction surface of MEIG1 and provide a framework to explore how MEIG1 recruits proteins to build the sperm tail.