ERM蛋白识别NHERF的结构基础。
Structural basis for NHERF recognition by ERM proteins.
作者信息
Terawaki Shin-ichi, Maesaki Ryoko, Hakoshima Toshio
机构信息
Structural Biology Laboratory, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
出版信息
Structure. 2006 Apr;14(4):777-89. doi: 10.1016/j.str.2006.01.015.
The Na+/H+ exchanger regulatory factor (NHERF) is a key adaptor protein involved in the anchoring of ion channels and receptors to the actin cytoskeleton through binding to ERM (ezrin/radixin/moesin) proteins. NHERF binds the FERM domain of ERM proteins, although NHERF has no signature Motif-1 sequence for FERM binding found in adhesion molecules. The crystal structures of the radixin FERM domain complexed with the NHERF-1 and NHERF-2 C-terminal peptides revealed a peptide binding site of the FERM domain specific for the 13 residue motif MDWxxxxx(L/I)Fxx(L/F) (Motif-2), which is distinct from Motif-1. This Motif-2 forms an amphipathic alpha helix for hydrophobic docking to subdomain C of the FERM domain. This docking causes induced-fit conformational changes in subdomain C and affects binding to adhesion molecule peptides, while the two binding sites are not overlapped. Our studies provide structural paradigms for versatile ERM linkages between membrane proteins and the cytoskeleton.
钠/氢交换调节因子（NHERF）是一种关键的衔接蛋白，通过与ERM（埃兹蛋白/根蛋白/膜突蛋白）结合，参与将离子通道和受体锚定到肌动蛋白细胞骨架上。NHERF与ERM蛋白的FERM结构域结合，尽管在黏附分子中未发现NHERF具有用于FERM结合的特征性基序1序列。与NHERF-１和NHERF-２ C末端肽复合的根蛋白FERM结构域的晶体结构揭示了FERM结构域针对13个残基基序MDWxxxxx(L/I)Fxx(L/F)（基序2）的肽结合位点，该基序与基序1不同。这个基序2形成一个两亲性α螺旋，用于与FERM结构域的C亚结构域进行疏水对接。这种对接会导致C亚结构域发生诱导契合构象变化，并影响与黏附分子肽的结合，而这两个结合位点并不重叠。我们的研究为膜蛋白和细胞骨架之间多样的ERM连接提供了结构范例。
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