Structural basis of cargo recognition by the myosin-X MyTH4-FERM domain.
Structural basis of cargo recognition by the myosin-X MyTH4-FERM domain.
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DOI：
10.1038/emboj.2011.177
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发表时间：
2011-06-03
期刊：
影响因子：
11.4
通讯作者：
Hakoshima, Toshio
中科院分区：
文献类型：
--
作者：
Hirano, Yoshinori;Hatano, Taiki;Takahashi, Aya;Toriyama, Michinori;Inagaki, Naoyuki;Hakoshima, Toshio
肌球蛋白-X是一种重要的非常规肌球蛋白，其对于将货物运输到丝状伪足尖端至关重要，并且还通过与微管相互作用而用于纺锤体组装。我们提出了一系列的肌球蛋白-X尾结构域盒的结构和生化研究，肌球蛋白尾同源4（MyTH 4）和FERM结构域与其特定的货物，netrin受体DCC（在结直肠癌中删除）的复合物。MyTH 4结构域折叠成螺旋状VHS样结构，并与FERM结构域相关。我们发现了DCC肽与FERM结构域的亚结构域C沟的意外结合模式，这与先前报道的在根蛋白-粘附分子复合物中发现的β-β缔合不同。我们还揭示了MyTH 4-FERM盒和微管蛋白C-末端酸性尾之间的直接相互作用，并鉴定了MyTH 4结构域的带正电荷的补丁，其参与微管蛋白结合。我们证明了DCC和整合素结合都干扰微管结合，DCC结合干扰整合素结合。我们的研究结果提供了肌球蛋白-X促进货物和微管的替代性双重结合的分子基础。
Myosin-X is an important unconventional myosin that is critical for cargo transportation to filopodia tips and is also utilized in spindle assembly by interacting with microtubules. We present a series of structural and biochemical studies of the myosin-X tail domain cassette, consisting of myosin tail homology 4 (MyTH4) and FERM domains in complex with its specific cargo, a netrin receptor DCC (deleted in colorectal cancer). The MyTH4 domain is folded into a helical VHS-like structure and is associated with the FERM domain. We found an unexpected binding mode of the DCC peptide to the subdomain C groove of the FERM domain, which is distinct from previously reported β–β associations found in radixin–adhesion molecule complexes. We also revealed direct interactions between the MyTH4–FERM cassette and tubulin C-terminal acidic tails, and identified a positively charged patch of the MyTH4 domain, which is involved in tubulin binding. We demonstrated that both DCC and integrin bindings interfere with microtubule binding and that DCC binding interferes with integrin binding. Our results provide the molecular basis by which myosin-X facilitates alternative dual binding to cargos and microtubules.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
64.5
作者：
Chan, SSY;Zheng, H;Culotti, JG
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影响因子：
3.3
作者：
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影响因子：
3.3
作者：
Berg, JS;Powell, BC;Cheney, RE
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Cheney, RE
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC