Forrest L R, DeGrado W F, Dieckmann G R, Sansom M S
Department of Biochemistry, University of Oxford, UK.
Fold Des. 1998;3(6):443-8. doi: 10.1016/S1359-0278(98)00061-3.
The influenza M2 protein is a simple membrane protein, containing a single transmembrane helix. It is representative of a very large family of single-transmembrane helix proteins. The functional protein is a tetramer, with the four transmembrane helices forming a proton-permeable channel across the bilayer. Two independently derived models of the M2 channel domain are compared, in order to assess the success of applying molecular modelling approaches to simple membrane proteins.
The Calpha RSMD between the two models is 1.7 A. Both models are composed of a left-handed bundle of helices, with the helices tilted roughly 15 degrees relative to the (presumed) bilayer normal. The two models have similar pore radius profiles, with a pore cavity lined by the Ser31 and Gly34 residues and a pore constriction formed by the ring of His37 residues.
Independent studies of M2 have converged on the same structural model for the channel domain. This model is in agreement with solid state NMR data. In particular, both model and NMR data indicate that the M2 helices are tilted relative to the bilayer normal and form a left-handed bundle. Such convergence suggests that, at least for simple membrane proteins, restraints-directed modelling might yield plausible models worthy of further computational and experimental investigation.
流感病毒M2蛋白是一种简单的膜蛋白，含有一个单一的跨膜螺旋。它是非常大的单跨膜螺旋蛋白家族的代表。功能性蛋白是一种四聚体，四个跨膜螺旋形成一个穿过双层膜的质子可渗透通道。比较了M2通道结构域的两个独立推导模型，以评估将分子建模方法应用于简单膜蛋白的成功程度。
两个模型之间的CαRSMD为1.7埃。两个模型均由左旋螺旋束组成，螺旋相对于（假定的）双层法线大致倾斜15度。两个模型具有相似的孔半径分布，孔腔由Ser31和Gly34残基排列，孔收缩由His37残基环形成。
对M2的独立研究已得出通道结构域的相同结构模型。该模型与固态NMR数据一致。特别是，模型和NMR数据均表明M2螺旋相对于双层法线倾斜并形成左旋束。这种趋同表明，至少对于简单的膜蛋白，约束导向建模可能会产生值得进一步进行计算和实验研究的合理模型。
