Structural Analysis of Human Cofilin 2/Filamentous Actin Assemblies: Atomic-Resolution Insights from Magic Angle Spinning NMR Spectroscopy
Date
2017-03-17
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Nature Publishing Group
Abstract
Cellular actin dynamics is an essential element of numerous cellular processes, such as cell motility,
cell division and endocytosis. Actin’s involvement in these processes is mediated by many actinbinding
proteins, among which the cofilin family plays unique and essential role in accelerating actin
treadmilling in filamentous actin (F-actin) in a nucleotide-state dependent manner. Cofilin preferentially
interacts with older filaments by recognizing time-dependent changes in F-actin structure associated
with the hydrolysis of ATP and release of inorganic phosphate (Pi) from the nucleotide cleft of actin. The
structure of cofilin on F-actin and the details of the intermolecular interface remain poorly understood
at atomic resolution. Here we report atomic-level characterization by magic angle spinning (MAS)
NMR of the muscle isoform of human cofilin 2 (CFL2) bound to F-actin. We demonstrate that resonance
assignments for the majority of atoms are readily accomplished and we derive the intermolecular
interface between CFL2 and F-actin. The MAS NMR approach reported here establishes the foundation
for atomic-resolution characterization of a broad range of actin-associated proteins bound to F-actin.
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Yehl, J. et al. Structural Analysis of Human Cofilin 2/Filamentous Actin Assemblies: Atomic-Resolution Insights from Magic Angle Spinning NMR Spectroscopy. Sci. Rep. 7, 44506; doi: 10.1038/ srep44506 (2017).