Nikiforovich G V, Galaktionov S, Balodis J, Marshall G R
Department of Biochemistry and Molecular Biophysics, Washington University, St. Louis, MO 63110, USA.
Acta Biochim Pol. 2001;48(1):53-64.
G-protein coupled receptors (GPCRs) are thought to be proteins with 7-membered transmembrane helical bundles (7TM proteins). Recently, the X-ray structures have been solved for two such proteins, namely for bacteriorhodopsin (BR) and rhodopsin (Rh), the latter being a GPCR. Despite similarities, the structures are different enough to suggest that 3D models for different GPCRs cannot be obtained directly employing 3D structures of BR or Rh as a unique template. The approach to computer modeling of 7TM proteins developed in this work was capable of reproducing the experimental X-ray structure of BR with great accuracy. A combination of helical packing and low-energy conformers for loops most close to the X-ray structure possesses the r.m.s.d. value of 3.13 A. Such a level of accuracy for the 3D-structure prediction for a 216-residue protein has not been achieved, so far, by any available ab initio procedure of protein folding. The approach may produce also other energetically consistent combinations of helical bundles and loop conformers, creating a variety of possible templates for 3D structures of 7TM proteins, including GPCRs. These templates may provide experimentalists with various plausible options for 3D structure of a given GPCR; in our view, only experiments will determine the final choice of the most reasonable 3D template.
G蛋白偶联受体（GPCRs）被认为是具有七元跨膜螺旋束的蛋白质（7TM蛋白）。最近，已经解析出了两种此类蛋白质的X射线结构，即细菌视紫红质（BR）和视紫红质（Rh），后者是一种GPCR。尽管存在相似性，但这些结构差异足以表明，不能直接将BR或Rh的三维结构作为唯一模板来获得不同GPCR的三维模型。本研究中开发的7TM蛋白计算机建模方法能够极其精确地重现BR的实验X射线结构。螺旋堆积和最接近X射线结构的环的低能构象的组合，其均方根偏差（r.m.s.d.）值为3.13埃。对于一个216个残基的蛋白质的三维结构预测，这样的精度水平是目前任何可用的蛋白质折叠从头算程序都尚未达到的。该方法还可能产生其他能量上一致的螺旋束和环构象组合，为包括GPCR在内的7TM蛋白的三维结构创建各种可能的模板。这些模板可以为实验人员提供给定GPCR三维结构的各种合理选项；在我们看来，只有实验才能确定最合理的三维模板的最终选择。
