Featured article (Research Highlights; Free Full text)
Biophysical Journal Volume 103 July 2012 275–283
Molecular Cooperativity of Drebrin1-300 Binding and Structural Remodeling of F-Actin
Shivani Sharma,†‡* Elena E. Grintsevich,† Carlin Hsueh,† Emil Reisler,†§ and James K. Gimzewski†‡{*
†Department of Chemistry and Biochemistry, ‡California NanoSystems Institute, and §Molecular Biology Institute, University of California, Los Angeles, California; and {International Center for Materials, Nanoarchitectonics Satellite, National Institute for Materials Science, Tsukuba, Japan
Drebrin A, an actin-binding protein, is a key regulatory element in synaptic plasticity of neuronal dendrites. Under- standing how drebrin binds and remodels F-actin is important for a functional analysis of their interactions. Conventionally, molecular models for protein-protein interactions use binding parameters derived from bulk solution measurements with limited spatial resolution, and the inherent assumption of homogeneous binding sites. In the case of actin filaments, their structural and dynamic states—as well as local changes in those states—may influence their binding parameters and interaction cooperativity. Here, we probed the structural remodeling of single actin filaments and the binding cooperativity of DrebrinA1-300 –F–actin using AFM imaging. We show direct evidence of DrebrinA1-300-induced cooperative changes in the helical structure of F-actin and observe the binding cooperativity of drebrin to F-actin with nanometer resolution. The data confirm at the in vitro molecular level that variations in the F-actin helical structure can be modulated by cooperative binding of actin-binding proteins.
*Correspondence: sharmas@ucla.edu or gim@chem.ucla.edu