Srinivasan R, Rose G D
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110.
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11113-7. doi: 10.1073/pnas.91.23.11113.
The relationship between the T, R, and R2 quaternary forms of hemoglobin is examined by computational experiments. Contrary to previous suggestions, we propose that the R quaternary form may lie on the pathway from T to R2. This proposal is consistent with four independent observations. (i) Difference distance maps are used to identify those parts of the molecule that undergo conformational change upon oxygenation. The simplest interpretation of these maps brackets R between T and R2. (ii) Linear interpolation from T to R2 passes through R. (iii) The well-known "switch" region (so called because, upon transition between the T and R quaternary forms, a residue from the beta 2 subunit toggles between two stable positions within the alpha 1 subunit) progresses from T through R to R2, successively. (iv) A hitherto-undocumented feature, diagnostic of the R structure, is noted within the alpha subunit: upon transformation from T to R, the beta-turns at the amino terminal of the E and F helices flip from one turn type to another. Upon transformation from R to R2, the latter turn--a strained conformation--flips back again.
通过计算实验研究了血红蛋白的T、R和R2四级结构形式之间的关系。与之前的观点相反，我们提出R四级结构形式可能位于从T到R2的途径上。这一观点与四项独立的观察结果一致。（i）差异距离图用于识别分子中在氧合时发生构象变化的部分。对这些图的最简单解释是将R置于T和R2之间。（ii）从T到R2的线性插值经过R。（iii）著名的“开关”区域（之所以这样称呼，是因为在T和R四级结构形式之间转换时，β2亚基的一个残基在α1亚基内的两个稳定位置之间切换）依次从T经过R到R2。（iv）在α亚基内发现了一个迄今未记录的、可诊断R结构的特征：从T转变为R时，E和F螺旋氨基末端的β转角从一种转角类型翻转到另一种。从R转变为R2时，后一种转角——一种应变构象——又翻转回来。
