Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine of NYU, New York, New York 10029, USA.
Phys Rev Lett. 2011 Jun 17;106(24):248101. doi: 10.1103/PhysRevLett.106.248101. Epub 2011 Jun 14.
The existence of conformational switching in proteins, induced by single amino acid mutations, presents an important challenge to our understanding of the physics of protein folding. Sequence-local methods, commonly used to detect structural homology, are incapable of accounting for this phenomenon. We examine a set of proteins, derived from the G(A) and G(B) domains of Streptococcus protein G, which are known to show a dramatic conformational change as a result of single-residue replacement. It is shown that these sequences, which are almost identical locally, can have very different global patterns of physical properties. These differences are consistent with the observed complete change in conformation. These results suggest that sequence-local methods for identifying structural homology can be misleading. They point to the importance of global sequence analysis in understanding sequence-structure relationships.
蛋白质构象转换的存在，由单个氨基酸突变诱导，对我们理解蛋白质折叠的物理学提出了重要挑战。常用于检测结构同源性的序列局部方法无法解释这种现象。我们研究了一组蛋白质，它们来自于链球菌蛋白 G 的 G(A)和 G(B)结构域，已知这些蛋白质由于单个残基的替换而表现出显著的构象变化。结果表明，这些序列在局部上几乎相同，但它们的全局物理特性模式可能非常不同。这些差异与观察到的构象完全变化一致。这些结果表明，用于识别结构同源性的序列局部方法可能具有误导性。它们指出了在理解序列结构关系时进行全局序列分析的重要性。
