Molecular conformation of the full-length tumor suppressor NF2/Merlin--a small-angle neutron scattering study.
Molecular conformation of the full-length tumor suppressor NF2/Merlin--a small-angle neutron scattering study.
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DOI：
10.1016/j.jmb.2014.05.011
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发表时间：
2014-07-29
影响因子：
5.6
通讯作者：
Bu Z
中科院分区：
文献类型：
--
作者：
Ali Khajeh J;Ju JH;Atchiba M;Allaire M;Stanley C;Heller WT;Callaway DJ;Bu Z
肿瘤抑制蛋白Merlin在建立细胞-细胞接触时抑制细胞增殖。由于Merlin与Ezrin-Radisin-Moesin(ERM)家族蛋白质具有很高的序列相似性，ERM蛋白的自抑制和在关闭/静止和开放/活动构象之间循环的结构模型经常被用来解释Merlin的功能。然而，最近的生化研究提出了Merlin功能的另一种分子模型。在这里，我们通过小角中子散射(SANS)和结合实验确定了Merlin和一个模拟S518处失活磷酸化的Merlin(S518D)突变体的低分辨分子结构和结合活性。SANS表明，在溶液中，Merlin和Merlin(S518D)都采用封闭构象，但结合实验表明，Merlin或Merlin(S518D)的很大一部分能够与靶蛋白NHERF1结合。与磷脂酰肌醇4，5-二磷酸脂结合后，野生型Merlin的构象比在溶液中更开放，而Merlin(S518D)保持封闭的构象。本研究支持Merlin在NHERF1结合中的变阻器模型，并有助于解决关于Merlin分子构象和结合活性的争议。
The tumor suppressor protein Merlin inhibits cell proliferation upon establishing cell-cell contacts. Because Merlin has high sequence similarity to the Ezrin-Radixin-Moesin (ERM) family of proteins, the structural model of ERM protein autoinhibition and cycling between closed/resting and open/active conformational states is often employed to explain Merlin function. However, recent biochemical studies suggest alternative molecular models of Merlin function. Here, we have determined the low resolution molecular structure and binding activity of Merlin and a Merlin(S518D) mutant that mimics the inactivating phosphorylation at S518 using small angle neutron scattering (SANS) and binding experiments. SANS shows that in solution both Merlin and Merlin(S518D) adopt a closed conformation, but binding experiments indicate that a significant fraction of either Merlin or Merlin(S518D) is capable of binding to the target protein NHERF1. Upon binding to the phosphatidylinositol 4,5-bisphosphate lipid, the wild-type Merlin adopts a more open conformation than in solution, but Merlin(S518D) remains in a closed conformation. This study supports a rheostat model of Merlin in NHERF1 binding, and contributes to resolve a controversy about the molecular conformation and binding activity of Merlin.
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磷酸肌醇的结合和磷酸化在ezrin的激活机理中依次起作用。
影响因子：
7.8
作者：
Fievet, BT;Gautreau, A;Roy, C;Del Maestro, L;Mangeat, P;Louvard, D;Arpin, M
通讯作者：
Arpin, M
DOI：
10.1073/pnas.0503388102
发表时间：
2005-12-06
影响因子：
11.1
作者：
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通讯作者：
Callaway, DJE
影响因子：
4.8
作者：
Kissil, JL;Johnson, KC;Jacks, T
通讯作者：
Jacks, T
影响因子：
5.3
作者：
Hennigan, Robert F.;Foster, Lauren A.;Ip, Wallace
通讯作者：
Ip, Wallace
影响因子：
3.4
作者：
Farago, Bela;Li, Jianquan;Bu, Zimei
通讯作者：
Bu, Zimei