Martínez J C, Serrano L
EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Nat Struct Biol. 1999 Nov;6(11):1010-6. doi: 10.1038/14896.
The protein engineering analysis of the alpha-spectrin SH3 domain at three different stability conditions (pH 7.0, 3.5 and 2.5) reveals a folding transition state structured around the distal loop beta-hairpin and the 310-helix. This region is impervious to overall changes in protein stability, suggesting a transition state ensemble with little conformational variability. Comparison with the Src SH3 domain (36% sequence homology) indicates that the transition state in this protein family may be conserved. Discrepancies at some positions can be rationalized in terms of the different interactions made by the different side chains in both domains. Brønsted plot analysis confirms the straight phi(doubledagger-U) results and shows two folding subdomains for this small protein. These results, together with previous data on circular permutants of the alpha-spectrin SH3 domain, indicate that polypeptide topology and chain connectivity play a major role in the folding reaction of this protein family.
在三种不同稳定性条件（pH 7.0、3.5和2.5）下对α-血影蛋白SH3结构域进行的蛋白质工程分析表明，其折叠过渡态围绕远端环β-发夹和310螺旋构建。该区域不受蛋白质稳定性整体变化的影响，这表明过渡态集合的构象变异性很小。与Src SH3结构域（序列同源性为36%）的比较表明，该蛋白质家族中的过渡态可能是保守的。某些位置的差异可以根据两个结构域中不同侧链形成的不同相互作用来解释。布伦斯台德图分析证实了直接的φ（双匕首-U）结果，并显示了这个小蛋白质的两个折叠亚结构域。这些结果，连同先前关于α-血影蛋白SH3结构域环形置换体的数据，表明多肽拓扑结构和链连接性在该蛋白质家族的折叠反应中起主要作用。
