Riddle D S, Santiago J V, Bray-Hall S T, Doshi N, Grantcharova V P, Yi Q, Baker D
Department of Biochemistry, University of Washington, Seattle 98195, USA.
Nat Struct Biol. 1997 Oct;4(10):805-9. doi: 10.1038/nsb1097-805.
Early protein synthesis is thought to have involved a reduced amino acid alphabet. What is the minimum number of amino acids that would have been needed to encode complex protein folds similar to those found in nature today? Here we show that a small beta-sheet protein, the SH3 domain, can be largely encoded by a five letter amino acid alphabet but not by a three letter alphabet. Furthermore, despite the dramatic changes in sequence, the folding rates of the reduced alphabet proteins are very close to that of the naturally occurring SH3 domain. This finding suggests that despite the vast size of the search space, the rapid folding of biological sequences to their native states is not the result of extensive evolutionary optimization. Instead, the results support the idea that the interactions which stabilize the native state induce a funnel shape to the free energy landscape sufficient to guide the folding polypeptide chain to the proper structure.
早期的蛋白质合成被认为涉及一个缩小的氨基酸字母表。要编码与当今自然界中发现的类似的复杂蛋白质折叠，所需的氨基酸的最小数量是多少？在这里，我们表明一种小的β-折叠蛋白，即SH3结构域，可以很大程度上由一个五字母的氨基酸字母表编码，但不能由一个三字母的字母表编码。此外，尽管序列发生了巨大变化，但简化字母表蛋白质的折叠速率与天然存在的SH3结构域的折叠速率非常接近。这一发现表明，尽管搜索空间巨大，但生物序列快速折叠成其天然状态并非广泛进化优化的结果。相反，这些结果支持这样一种观点，即稳定天然状态的相互作用会在自由能景观中诱导出一个漏斗形状，足以引导折叠的多肽链形成正确的结构。
