Conformational Dynamics of Actin Family Proteins

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Abstract/Contents

Abstract: The actin family of cytoskeletal proteins is essential to the physiology of virtually all archaea, bacteria, and eukaryotes. While X-ray crystallography and electron microscopy have revealed structural homologies among actin-family proteins, these techniques cannot probe molecular-scale conformational dynamics. Here, we use long- time scale, all-atom molecular dynamic simulations to reveal conserved dynamical behaviors in four prokaryotic actin homologs: MreB, FtsA, ParM, and crenactin. We demonstrate that the majority of the conformational dynamics of prokaryotic actins can be explained by treating the four subdomains as rigid bodies. MreB, ParM, and FtsA monomers exhibited nucleotide-dependent dihedral and opening angles, while crenactin monomer dynamics were nucleotide-independent. We further determine that the opening angle of ParM is sensitive to a specific interaction between subdomains. Steered molecular dynamics simulations of MreB, FtsA, and crenactin dimers revealed that changes in subunit dihedral angle lead to intersubunit bending or twist, suggesting a conserved mechanism for regulating filament structure. Taken together, our results provide molecular-scale insights into the nucleotide and polymerization dependencies of the structure of prokaryotic actins. Using these results, we propose a proof of concept design workflow, where we use properties of atomistic MreB simulations to design mutants with tuned dihedral and opening angles.

Type of resource	text
Date created	May 25, 2018

Author	Ng, Natalie
Primary advisor	Huang, Kerwyn
Advisor	Colavin, Alexandre
Degree granting institution	Stanford University, Department of Bioengineering

Location	https://purl.stanford.edu/xw490gx7725

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License: This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

Preferred Citation: Ng, Natalie. (2018). Conformational Dynamics of Actin Family Proteins. Stanford Digital Repository. Available at: https://purl.stanford.edu/xw490gx7725

Undergraduate Theses, School of Engineering

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