title: Molecular cooperativity of drebrin1-300 binding and structural remodeling of F-actin.
abstract: Drebrin A, an actin-binding protein, is a key regulatory element in synaptic plasticity of neuronal dendrites. Understanding 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 DrebrinA(1-300) -F-actin using AFM imaging. We show direct evidence of DrebrinA(1-300)-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.
authors.affiliation: Department of Chemistry, University of California, Los Angeles, California, USA. sharmas@ucla.edu
authors.forename: Shivani
authors.initials: S
authors.lastname: Sharma
authors.forename: Elena E
authors.initials: EE
authors.lastname: Grintsevich
authors.forename: Carlin
authors.initials: C
authors.lastname: Hsueh
authors.forename: Emil
authors.initials: E
authors.lastname: Reisler
authors.forename: James K
authors.initials: JK
authors.lastname: Gimzewski
mesh_terms: D008841:Actin Cytoskeleton; D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D018625:Microscopy, Atomic Force; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D050505:Mutant Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D000199:Actins; D050505:Mutant Proteins; D009479:Neuropeptides; C053386:drebrins