Laboratory of Physical Chemistry, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093, Zürich, Switzerland.
Eur Biophys J. 2013 Mar;42(2-3):181-97. doi: 10.1007/s00249-012-0802-z. Epub 2012 May 3.
Secondary active transporters from several protein families share a core of two five-helix inverted repeats that has become known as the LeuT fold. The known high-resolution protein structures with this fold were analyzed by structural superposition of the core transmembrane domains (TMDs). Three angle parameters derived from the mean TMD axes correlate with accessibility of the central binding site from the outside or inside. Structural transitions between distinct conformations were analyzed for four proteins in terms of changes in relative TMD arrangement and in internal conformation of TMDs. Collectively moving groups of TMDs were found to be correlated in the covariance matrix of elastic network models. The main features of the structural transitions can be reproduced with the 5 % slowest normal modes of anisotropic elastic network models. These results support the rocking bundle model for the major conformational change between the outward- and inward-facing states of the protein and point to an important role for the independently moving last TMDs of each repeat in occluding access to the central binding site. Occlusion is also supported by flexing of some individual TMDs in the collectively moving bundle and hash motifs.
几种蛋白家族的次级主动转运蛋白共享由两个五螺旋反向重复组成的核心，这个核心被称为 LeuT 折叠。对具有这种折叠的已知高分辨率蛋白质结构进行了核心跨膜结构域（TMD）的结构叠加分析。从平均 TMD 轴导出的三个角度参数与从外部或内部进入中央结合位点的可达性相关。对四个蛋白质的不同构象之间的结构转换进行了分析，涉及 TMD 相对排列的变化和 TMD 内部构象的变化。在弹性网络模型的协方差矩阵中发现，整体移动的 TMD 组之间存在相关性。主要结构转换的特征可以用各向异性弹性网络模型中最慢的 5%慢模来再现。这些结果支持了蛋白向外和向内构象之间的主要构象变化的摇摆束模型，并指出每个重复中独立移动的最后一个 TMD 在阻塞中央结合位点的进入方面起着重要作用。封闭也得到了共同移动束和 hash 基序中一些单独 TMD 的弯曲的支持。
