F-actin is a helical assembly of actin, which is a component of muscle fibres essential for contraction and has a crucial role in numerous cellular processes, such as the formation of lamellipodia and filopodia1 as the most abundant component and regulator of cytoskeletons by dynamic assembly and disassembly (from G-actin to F-actin and vice versa). Actin is a ubiquitous protein and is involved in important biological functions, but the definitive high-resolution structure of F-actin remains unknown. Although a recent atomic model well reproduced X-ray fibre diffraction intensity data from a highly oriented liquid-crystalline sol specimen3, its refinement without experimental phase information has certain limitations. Direct visualization of the structure by electron cryomicroscopy, however, has been difficult because it is relatively thin and flexible. Here we report the F-actin structure at 6.6 Å resolution, made obtainable by recent advances in electron cryomicroscopy. The density map clearly resolves all the secondary structures of G-actin, such as α-helices, β-structures and loops, and makes unambiguous modelling and refinement possible. Complex domain motions that open the nucleotide-binding pocket on F-actin formation, specific D-loop and terminal conformations, and relatively tight axial but markedly loose interprotofilament interactions hydrophilic in nature are revealed in the F-actin model, and all seem to be important for dynamic functions of actin.
Electron microscopes can image biological macromolecules in cryogenic ice, but it shows them as low-contrast features in a grainy image (see below). Using enough electrons to reduce the graininess would first destroy the specimen.
The trick to getting enough information without frying the molecules is to image many specimens that are known to be identical, and to somehow find, align, and combine data from their images (keep in mind that these are grainy, 2D shadows of randomly oriented 3D objects). The quality of the resulting reconstruction depends heavily on the quality of the methods, and the methods are not simple.
A new report in Nature describes improved methods and a result (below) that sharpens resolution from the previous 1.3 nm to 0.66 nm. This provides about 8 times as many voxels, and gave the authors enough information to infer protein secondary structures and build a reliable atomic model of F-actin
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