Effects of polymerization and nucleotide identity on the conformational dynamics of the bacterial actin homolog MreB

Proceedings of the National Academy of Sciences of the United States of America
Alexandre ColavinKerwyn Casey Huang

Abstract

The assembly of protein filaments drives many cellular processes, from nucleoid segregation, growth, and division in single cells to muscle contraction in animals. In eukaryotes, shape and motility are regulated through cycles of polymerization and depolymerization of actin cytoskeletal networks. In bacteria, the actin homolog MreB forms filaments that coordinate the cell-wall synthesis machinery to regulate rod-shaped growth and contribute to cellular stiffness through unknown mechanisms. Like actin, MreB is an ATPase and requires ATP to polymerize, and polymerization promotes nucleotide hydrolysis. However, it is unclear whether other similarities exist between MreB and actin because the two proteins share low sequence identity and have distinct cellular roles. Here, we use all-atom molecular dynamics simulations to reveal surprising parallels between MreB and actin structural dynamics. We observe that MreB exhibits actin-like polymerization-dependent structural changes, wherein polymerization induces flattening of MreB subunits, which restructures the nucleotide-binding pocket to favor hydrolysis. MreB filaments exhibited nucleotide-dependent intersubunit bending, with hydrolyzed polymers favoring a straighter conformation. ...Continue Reading

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Citations

May 21, 2014·ELife·Fusinita van den EntJan Löwe
Oct 22, 2015·Annual Review of Microbiology·Ned S Wingreen, Kerwyn Casey Huang
Mar 3, 2018·Soft Matter·Min-Kyung ChaeNam-Kyung Lee
Mar 31, 2018·Nature Communications·Alexandre ColavinKerwyn Casey Huang
Apr 6, 2019·PLoS Computational Biology·Natalie NgKerwyn Casey Huang
Jul 21, 2020·Scientific Reports·Dávid SzatmáriMiklós Nyitrai
Jan 31, 2020·Frontiers in Chemistry·Elvis Awuni
Jul 20, 2018·Nature Communications·Benjamin P BrattonRandy M Morgenstein
Mar 18, 2020·Nature Communications·Handuo ShiKerwyn Casey Huang
May 18, 2020·Biophysical Journal·John N WernerEric A Klein
Jun 30, 2021·Annual Review of Cell and Developmental Biology·Ethan C Garner
Nov 16, 2018··A.K. SurinA.V. Glyakina

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