Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA.
Nat Struct Mol Biol. 2010 Nov;17(11):1318-23. doi: 10.1038/nsmb.1930. Epub 2010 Oct 10.
Actin has maintained an exquisite degree of sequence conservation over large evolutionary distances for reasons that are not understood. The desire to explain phenomena from muscle contraction to cytokinesis in mechanistic detail has driven the generation of an atomic model of the actin filament (F-actin). Here we use electron cryomicroscopy to show that frozen-hydrated actin filaments contain a multiplicity of different structural states. We show (at ∼10 Å resolution) that subdomain 2 can be disordered and can make multiple contacts with the C terminus of a subunit above it. We link a number of disease-causing mutations in the human ACTA1 gene to the most structurally dynamic elements of actin. Because F-actin is structurally polymorphic, it cannot be described using only one atomic model and must be understood as an ensemble of different states.
肌动蛋白在很大的进化距离上保持了高度的序列保守性，其原因尚不清楚。人们渴望从肌肉收缩到胞质分裂等现象的角度，以机械细节的方式来解释这些现象，这推动了肌动蛋白丝（F-actin）原子模型的产生。在这里，我们使用电子 cryomicroscopy 来显示冷冻水合肌动蛋白丝包含多种不同的结构状态。我们表明（在约 10 Å 分辨率下）亚结构域 2 可以是无序的，并可以与位于其上的亚基的 C 末端进行多次接触。我们将人类 ACTA1 基因中的许多致病突变与肌动蛋白最具结构动态的元素联系起来。由于 F-actin 在结构上是多态的，因此不能只用一个原子模型来描述，而必须被理解为不同状态的集合。
