A change in actin conformation associated with filament instability after Pi release
A change in actin conformation associated with filament instability after Pi release
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DOI：
10.1073/pnas.96.1.29
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发表时间：
1999-01-05
影响因子：
11.1
通讯作者：
Egelman, EH
中科院分区：
文献类型：
--
作者：
Belmont, LD;Orlova, A;Egelman, EH
肌动蛋白既能聚合成丝又能解聚的能力使得肌动蛋白结构能够快速重排，这对肌动蛋白在大多数细胞过程中的功能至关重要。肌动蛋白丝上的ATP水解赋予了丝的极性和动态特性。ATP水解后从丝上释放无机磷酸盐（Pi）促进解聚。我们鉴定出一种酵母肌动蛋白突变，即缬氨酸159变为天冬酰胺，它使Pi释放与导致丝不稳定的构象变化解偶联。电子显微照片的三维重建揭示了ADP - Pi丝和ADP丝之间的构象差异，并表明ADP V159N丝类似于ADP - Pi野生型丝。哺乳动物β - 肌动蛋白的核苷酸结合裂隙处于“开放”和“关闭”状态的晶体结构可分别用于模拟ADP和ADP - Pi构象的肌动蛋白丝。我们提出，G - 肌动蛋白的这两种构象可能与F - 肌动蛋白的两种功能状态有关。
The ability of actin to both polymerize into filaments and to depolymerize permits the rapid rearrangements of actin structures that are essential for actin's function in most cellular processes. Filament polarity and dynamic properties are conferred by the hydrolysis of ATP on actin filaments. Release of inorganic phosphate (P-i) from filaments after ATP hydrolysis promotes depolymerization. We identify a yeast actin mutation, Val-159 to Asn, which uncouples P-i release from the conformational change that results in filament destabilization. Three-dimensional reconstructions of electron micrographs reveal a conformational difference between ADP-P-i filaments and ADP filaments and show that ADP V159N filaments resemble ADP-P-i wild-type filaments. Crystal structures of mammalian beta-actin in which the nucleotide binding cleft is in the "open" and "closed" states can be used to model actin filaments in the ADP and ADP-P-i conformations, respectively. We propose that these two conformations of G-actin may be related to two functional states of F-actin.