Structural basis for polarized elongation of actin filaments.

Autor:	Zsolnay V; Graduate Program in Biophysical Sciences, University of Chicago, Chicago, IL 60637., Katkar HH; Department of Chemistry, University of Chicago, Chicago, IL 60637.; Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637.; James Franck Institute, University of Chicago, Chicago, IL 60637., Chou SZ; Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103., Pollard TD; Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8103.; Department of Cell Biology, Yale University, New Haven, CT 06520-8103., Voth GA; Department of Chemistry, University of Chicago, Chicago, IL 60637; gavoth@uchicago.edu.; Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637.; James Franck Institute, University of Chicago, Chicago, IL 60637.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Dec 01; Vol. 117 (48), pp. 30458-30464. Date of Electronic Publication: 2020 Nov 16.
DOI:	10.1073/pnas.2011128117
Abstrakt:	Actin filaments elongate and shorten much faster at their barbed end than their pointed end, but the molecular basis of this difference has not been understood. We use all-atom molecular dynamics simulations to investigate the properties of subunits at both ends of the filament. The terminal subunits tend toward conformations that resemble actin monomers in solution, while contacts with neighboring subunits progressively flatten the conformation of internal subunits. At the barbed end the terminal subunit is loosely tethered by its DNase-1 loop to the third subunit, because its monomer-like conformation precludes stabilizing contacts with the penultimate subunit. The motions of the terminal subunit make the partially flattened penultimate subunit accessible for binding monomers. At the pointed end, unique contacts between the penultimate and terminal subunits are consistent with existing cryogenic electron microscopic (cryo-EM) maps, limit binding to incoming monomers, and flatten the terminal subunit, which likely promotes ATP hydrolysis and rapid phosphate release. These structures explain the distinct polymerization kinetics of the two ends. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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