Nucleotide regulation of the structure and dynamics of G-actin

Marissa G. Saunders, Jeremy Tempkin, Jonathan Weare, Aaron R. Dinner, Benoît Roux, Gregory A. Voth

Research output: Contribution to journalArticlepeer-review


Actin, a highly conserved cytoskeletal protein found in all eukaryotic cells, facilitates cell motility and membrane remodeling via a directional polymerization cycle referred to as treadmilling. The nucleotide bound at the core of each actin subunit regulates this process. Although the biochemical kinetics of treadmilling has been well characterized, the atomistic details of how the nucleotide affects polymerization remain to be definitively determined. There is increasing evidence that the nucleotide regulation (and other characteristics) of actin cannot be fully described from the minimum energy structure, but rather depends on a dynamic equilibrium between conformations. In this work we explore the conformational mobility of the actin monomer (G-actin) in a coarse-grained subspace using umbrella sampling to bias all-atom molecular-dynamics simulations along the variables of interest. The results reveal that ADP-bound actin subunits are more conformationally mobile than ATP-bound subunits. We used a multiscale analysis method involving coarse-grained and atomistic representations of these simulations to characterize how the nucleotide affects the low-energy states of these systems. The interface between subdomains SD2-SD4, which is important for polymerization, is stabilized in an actin filament-like (F-actin) conformation in ATP-bound G-actin. Additionally, the nucleotide modulates the conformation of the SD1-SD3 interface, a region involved in the binding of several actin-binding proteins.

Original languageEnglish (US)
Pages (from-to)1710-1720
Number of pages11
JournalBiophysical journal
Issue number8
StatePublished - Apr 15 2014

ASJC Scopus subject areas

  • Biophysics


Dive into the research topics of 'Nucleotide regulation of the structure and dynamics of G-actin'. Together they form a unique fingerprint.

Cite this