ACF7 EF手型-甘氨酸-精氨酸模块的结构及微管结合决定因素的描述
Structure of the ACF7 EF-Hand-GAR Module and Delineation of Microtubule Binding Determinants.
作者信息
Lane Thomas R, Fuchs Elaine, Slep Kevin C
机构信息
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA; Molecular and Cellular Biophysics Program, University of North Carolina, Chapel Hill, NC 27599, USA.
Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA; Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.
出版信息
Structure. 2017 Jul 5;25(7):1130-1138.e6. doi: 10.1016/j.str.2017.05.006. Epub 2017 Jun 8.
Spectraplakins are large molecules that cross-link F-actin and microtubules (MTs). Mutations in spectraplakins yield defective cell polarization, aberrant focal adhesion dynamics, and dystonia. We present the 2.8 Å crystal structure of the hACF7 EF1-EF2-GAR MT-binding module and delineate the GAR residues critical for MT binding. The EF1-EF2 and GAR domains are autonomous domains connected by a flexible linker. The EF1-EF2 domain is an EFβ-scaffold with two bound Ca ions that straddle an N-terminal α helix. The GAR domain has a unique α/β sandwich fold that coordinates Zn. While the EF1-EF2 domain is not sufficient for MT binding, the GAR domain is and likely enhances EF1-EF2-MT engagement. Residues in a conserved basic patch, distal to the GAR domain's Zn-binding site, mediate MT binding.
光谱plakin是一种交联F-肌动蛋白和微管（MTs）的大分子。光谱plakin中的突变会导致细胞极化缺陷、异常的粘着斑动力学和肌张力障碍。我们展示了hACF7 EF1-EF2-GAR微管结合模块的2.8埃晶体结构，并确定了对微管结合至关重要的GAR残基。EF1-EF2和GAR结构域是由柔性接头连接的自主结构域。EF1-EF2结构域是一种EFβ支架，有两个结合的钙离子横跨一个N端α螺旋。GAR结构域有一个独特的α/β三明治折叠结构来配位锌。虽然EF1-EF2结构域不足以结合微管，但GAR结构域可以，并且可能增强EF1-EF2与微管的结合。在GAR结构域锌结合位点远端的一个保守碱性区域中的残基介导微管结合。
Zotero 插件