Gassner N C, Baase W A, Matthews B W
Institute of Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene 97403, USA.
Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12155-8. doi: 10.1073/pnas.93.22.12155.
To test whether the structure of a protein is determined in a manner akin to the assembly of a jigsaw puzzle, up to 10 adjacent residues within the core of T4 lysozyme were replaced by methionine. Such variants are active and fold cooperatively with progressively reduced stability. The structure of a seven-methionine variant has been shown, crystallographically, to be similar to wild type and to maintain a well ordered core. The interaction between the core residues is, therefore, not strictly comparable with the precise spatial complementarity of the pieces of a jigsaw puzzle. Rather, a certain amount of give and take in forming the core structure is permitted. A simplified hydrophobic core sequence, imposed without genetic selection or computer-based design, is sufficient to retain native properties in a globular protein.
为了测试蛋白质的结构是否以类似于拼图组装的方式确定，T4溶菌酶核心区域内多达10个相邻残基被甲硫氨酸取代。这些变体具有活性且能协同折叠，但稳定性逐渐降低。晶体学研究表明，一种含有七个甲硫氨酸的变体的结构与野生型相似，并保持了有序的核心结构。因此，核心残基之间的相互作用与拼图碎片精确的空间互补性并不严格可比。相反，在形成核心结构时允许一定程度的相互让步。在没有基因选择或基于计算机设计的情况下施加的简化疏水核心序列，足以在球状蛋白质中保留天然特性。
