Peng Tao, Zintsmaster John S, Namanja Andrew T, Peng Jeffrey W
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556 USA.
Nat Struct Mol Biol. 2007 Apr;14(4):325-31. doi: 10.1038/nsmb1207. Epub 2007 Mar 4.
The current canon attributes the binding specificity of protein-recognition motifs to distinctive chemical moieties in their constituent amino acid sequences. However, we show for a WW domain that the sequence crucial for specificity is an intrinsically flexible loop that partially rigidifies upon ligand docking. A single-residue deletion in this loop simultaneously reduces loop flexibility and ligand binding affinity. These results suggest that sequences of recognition motifs may reflect natural selection of not only chemical properties but also dynamic modes that augment specificity.
当前的标准观点认为，蛋白质识别基序的结合特异性归因于其组成氨基酸序列中独特的化学基团。然而，我们发现对于一个WW结构域而言，决定特异性的关键序列是一个内在柔性的环，该环在配体对接时会部分刚性化。此环中单个残基的缺失会同时降低环的柔性和配体结合亲和力。这些结果表明，识别基序的序列可能不仅反映了化学性质的自然选择，还反映了增强特异性的动态模式的自然选择。
