Shoemaker B A, Portman J J, Wolynes P G
Departments of Chemistry and Physics, University of Illinois, 600 South Mathews Avenue, Urbana, IL 61801, USA.
Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8868-73. doi: 10.1073/pnas.160259697.
Protein folding and binding are kindred processes. Many proteins in the cell are unfolded, so folding and function are coupled. This paper investigates how binding kinetics is influenced by the folding of a protein. We find that a relatively unstructured protein molecule can have a greater capture radius for a specific binding site than the folded state with its restricted conformational freedom. In this scenario of binding, the unfolded state binds weakly at a relatively large distance followed by folding as the protein approaches the binding site: the "fly-casting mechanism." We illustrate this scenario with the hypothetical kinetics of binding a single repressor molecule to a DNA site and find that the binding rate can be significantly enhanced over the rate of binding of a fully folded protein.
蛋白质折叠与结合是相关过程。细胞中的许多蛋白质是未折叠的，因此折叠与功能是相互关联的。本文研究了蛋白质折叠如何影响结合动力学。我们发现，一个相对无结构的蛋白质分子对于特定结合位点可能具有比构象自由度受限的折叠状态更大的捕获半径。在这种结合情况下，未折叠状态在相对较大距离处弱结合，随后随着蛋白质接近结合位点而折叠：即“抛锚机制”。我们用单个阻遏物分子与DNA位点结合的假设动力学来说明这种情况，发现结合速率可比完全折叠蛋白质的结合速率显著提高。
