Polymerization of actin into cytoskeletal filaments is coupled to its bound adenine nucleotides. The mechanism by which nucleotide modulates actin functions has not been evident from analyses of ATP- and ADP-bound crystal structures of the actin monomer. We report that NMR chemical shift differences between the two forms are globally distributed. Furthermore, microsecond–millisecond motions are spread throughout the molecule in the ATP form, but largely confined to subdomains 1 and 2, and the nucleotide binding site in the ADP form. Through these motions, the ATP- and ADP-bound forms sample different high-energy conformations. A deafness-causing, fast-nucleating actin mutant populates the high-energy conformer of ATP-actin more than the wild-type protein, suggesting that this conformer may be on the pathway to nucleation. Together, the data suggest a model in which differential sampling of a nucleation-compatible form of the actin monomer may contribute to control of actin filament dynamics by nucleotide.

肌动蛋白聚合成细胞骨架丝与其结合的腺嘌呤核苷酸偶联。从肌动蛋白单体的 ATP 和 ADP 结合晶体结构的分析中，核苷酸调节肌动蛋白功能的机制并不明显。我们报告说，这两种形式之间的 NMR 化学位移差异是全球分布的。此外，微秒-毫秒运动以 ATP 形式遍布整个分子，但主要局限于子域 1 和 2，以及 ADP 形式的核苷酸结合位点。通过这些运动，ATP 和 ADP 结合形式采样不同的高能构象。一种导致耳聋的快速成核肌动蛋白突变体比野生型蛋白质更多地填充 ATP 肌动蛋白的高能构象异构体，表明这种构象异构体可能在成核途径上。一起，