THE PROBABLE ARRANGEMENT OF THE HELICES IN G-PROTEIN-COUPLED RECEPTORS
THE PROBABLE ARRANGEMENT OF THE HELICES IN G-PROTEIN-COUPLED RECEPTORS
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DOI：
10.1002/j.1460-2075.1993.tb05814.x
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发表时间：
1993-04-01
期刊：
影响因子：
11.4
通讯作者：
BALDWIN, JM
中科院分区：
文献类型：
--
作者：
BALDWIN, JM
G蛋白偶联受体形成了一个完整的膜蛋白大家族，其氨基酸序列有七个疏水片段，包含独特的序列模式。视紫红质是该家族的成员之一，已知具有跨膜α螺旋。所有受体中七个螺旋的可能排列是从对序列的详细分析中提取的结构信息推断出来的。建立的限制包括：(1)每个螺旋必须位于序列中相邻的位置；(2)螺旋I、IV和V必须最容易接触受体周围的脂类，而螺旋III必须最少暴露。(1)是由最短回路的长度建立的。(2)是通过考虑以下因素确定的：(I)最保守残基的位点；(Ii)变异性受到限制的其他位点；(Iii)容纳极性残基的位点；(Iv)密切相关的受体对之间或组内序列差异的位点。最后一类中的大多数位置应该位于不重要的位置，并且在确定每个螺旋中面向脂质的表面的位置和范围方面最有用。受体的结构限制被用来将特定的螺旋分配给最近发表的视紫红质投影图中的峰，并提出G蛋白偶联受体中螺旋的试探性三维排列。
G protein-coupled receptors form a large family of integral membrane proteins whose amino acid sequences have seven hydrophobic segments containing distinctive sequence patterns. Rhodopsin, a member of the family, is known to have transmembrane alpha-helices. The probable arrangement of the seven helices, in all receptors, was deduced from structural information extracted from a detailed analysis of the sequences. Constraints established include: (1) each helix must be positioned next to its neighbours in the sequence; (2) helices I, IV and V must be most exposed to the lipid surrounding the receptor and helix III least exposed. (1) is established from the lengths of the shortest loops. (2) is determined by considering: (i) sites of the most conserved residues; (ii) other sites where variability is restricted; (iii) sites that accommodate polar residues; (iv) sites of differences in sequence between pairs or within groups of closely related receptors. Most sites in the last category should be in unimportant positions and are most useful in determining the position and extent of lipid-facing surface in each helix. The structural constraints for the receptors are used to allocate particular helices to the peaks in the recently published projection map of rhodopsin and to propose a tentative three-dimensional arrangement of the helices in G protein-coupled receptors.