Structural analyses of FERM domain-mediated membrane localization of FARP1.
Structural analyses of FERM domain-mediated membrane localization of FARP1.
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FERM 结构域介导的 FARP1 膜定位的结构分析
DOI：
10.1038/s41598-018-28692-4
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发表时间：
2018-07-11
影响因子：
4.6
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Kuo YC;He X;Coleman AJ;Chen YJ;Dasari P;Liou J;Biederer T;Zhang X
FARP1是一种多结构域蛋白，通过与细胞表面蛋白如a类丛蛋白和SynCAM 1相互作用参与调节神经元发育。已知FARP1的n端FERM结构域既促进膜定位又介导这些蛋白质相互作用，其潜在的分子机制尚不清楚。在这里，我们测定了斑马鱼中FARP1的FERM结构域，以及小鼠和斑马鱼中FARP2 （FARP1的近亲）的晶体结构。这些FERM域采用三叶三叶草折叠，这是所有FERM域的典型特征。我们的结构揭示了一个带正电的表面斑块，在FARP1和FARP2的FERM域中高度保守。体外脂质结合实验表明，FARP1 FERM结构域特异性结合几种类型的磷脂，这取决于带正电的表面斑块。我们进一步通过基于细胞的分析确定，FERM结构域的表面斑块是FARP1定位到质膜的基础，并且FERM结构域的相互作用将其招募到神经元的突触后位点。
FARP1 is a multi-domain protein that is involved in regulating neuronal development through interacting with cell surface proteins such as class A Plexins and SynCAM 1. The N-terminal FERM domain in FARP1 is known to both promote membrane localization and mediate these protein interactions, for which the underlying molecular mechanisms remain unclear. Here we determined the crystal structures of the FERM domain of FARP1 from zebrafish, and those of FARP2 (a close homolog of FARP1) from mouse and zebrafish. These FERM domains adopt the three-leaved clover fold that is typical of all FERM domains. Our structures reveal a positively charged surface patch that is highly conserved in the FERM domain of FARP1 and FARP2. In vitro lipid-binding experiments showed that the FARP1 FERM domain binds specifically to several types of phospholipid, which is dependent on the positively charged surface patch. We further determined through cell-based analyses that this surface patch on the FERM domain underlies the localization of FARP1 to the plasma membrane, and that FERM domain interactions recruit it to postsynaptic sites in neurons.
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影响因子：
5.3
作者：
Murata, Takaaki;Ohnishi, Hiroshi;Matozaki, Takashi
通讯作者：
Matozaki, Takashi
影响因子：
5.8
作者：
Gouet, P;Courcelle, E;Métoz, F
通讯作者：
Métoz, F
影响因子：
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作者：
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通讯作者：
Hallberg, B. Martin
影响因子：
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作者：
Takegahara, Noriko;Kang, Sujin;Kumanogoh, Atsushi
通讯作者：
Kumanogoh, Atsushi
影响因子：
25
作者：
Toyofuku, T;Yoshida, J;Kikutani, H
通讯作者：
Kikutani, H