Clarke J, Cota E, Fowler S B, Hamill S J
Department of Chemistry, Centre for Protein Engineering, University of Cambridge Lensfield Road, Cambridge, CB2 1EW, UK.
Structure. 1999 Sep 15;7(9):1145-53. doi: 10.1016/s0969-2126(99)80181-6.
Are folding pathways conserved in protein families? To test this explicitly and ask to what extent structure specifies folding pathways requires comparison of proteins with a common fold. Our strategy is to choose members of a highly diverse protein family with no conservation of function and little or no sequence identity, but with structures that are essentially the same. The immunoglobulin-like fold is one of the most common structural families, and is subdivided into superfamilies with no detectable evolutionary or functional relationship.
We compared the folding of a number of immunoglobulin-like proteins that have a common structural core and found a strong correlation between folding rate and stability. The results suggest that the folding pathways of these immunoglobulin-like proteins share common features.
This study is the first to compare the folding of structurally related proteins that are members of different superfamilies. The most likely explanation for the results is that interactions that are important in defining the structure of immunoglobulin-like proteins are also used to guide folding.
蛋白质家族中的折叠途径是保守的吗？为了明确测试这一点，并探究结构在多大程度上决定折叠途径，需要对具有相同折叠结构的蛋白质进行比较。我们的策略是选择一个高度多样化的蛋白质家族的成员，这些成员功能不保守，序列同一性很少或没有，但结构基本相同。免疫球蛋白样折叠是最常见的结构家族之一，并且被细分为没有可检测到的进化或功能关系的超家族。
我们比较了一些具有共同结构核心的免疫球蛋白样蛋白质的折叠情况，发现折叠速率与稳定性之间存在很强的相关性。结果表明，这些免疫球蛋白样蛋白质的折叠途径具有共同特征。
本研究首次比较了不同超家族成员中结构相关蛋白质的折叠情况。对结果最可能的解释是，在定义免疫球蛋白样蛋白质结构中起重要作用的相互作用也用于指导折叠。
