Division of Biology, Sir Alexander Fleming Building, Imperial College London, London SW7 2AZ, UK.
Mol Cell. 2012 Aug 10;47(3):484-90. doi: 10.1016/j.molcel.2012.06.012. Epub 2012 Jul 11.
AAA+ proteins (ATPases associated with various cellular activities) are oligomeric ATPases that use ATP hydrolysis to remodel their substrates. By similarity with GTPases, a dynamic organization of the nucleotide-binding pockets between ATPase protomers is proposed to regulate functionality. Using the transcription activator PspF as an AAA+ model, we investigated contributions of conserved residues for roles in ATP hydrolysis and intersubunit communication. We determined the R-finger residue and revealed that it resides in a conserved "R-hand" motif (R(x)D(xxx)R) needed for its "trans-acting" activity. Further, a divergent Walker A glutamic acid residue acts synergistically with a tyrosine residue to function in ADP-dependent subunit-subunit coordination, forming the "ADP-switch" motif. Another glutamic acid controls hexamer formation in the presence of nucleotides. Together, these results lead to a "residue-nucleotide" interaction map upon which to base AAA+ core regulation.
AAA+ 蛋白（与各种细胞活动相关的 ATP 酶）是多聚体 ATP 酶，利用 ATP 水解来重塑其底物。通过与 GTP 酶的相似性，提出核苷酸结合口袋在 ATP 酶亚基之间的动态组织来调节功能。使用转录激活因子 PspF 作为 AAA+ 模型，我们研究了保守残基对 ATP 水解和亚基间通讯作用的贡献。我们确定了 R 指残基，并揭示了它位于保守的“R 手”基序（R(x)D(xxx)R）中，这对于其“反式作用”活性是必需的。此外，一个发散的 Walker A 谷氨酸残基与酪氨酸残基协同作用，在 ADP 依赖性亚基-亚基协调中发挥作用，形成“ADP 开关”基序。另一个谷氨酸残基控制核苷酸存在时的六聚体形成。总之，这些结果导致了一个“残基-核苷酸”相互作用图，作为 AAA+ 核心调节的基础。
