title: Do the utrophin tandem calponin homology domains bind F-actin in a compact or extended conformation?
abstract: Tandem calponin-homology (CH) domains play an important role in the actin-binding function of many spectrin superfamily proteins. Crystal structures from several of these proteins have suggested a flexibility between these domains, and the manner in which these domains bind to F-actin has been the subject of some controversy. A recent paper has used electron microscopy and three-dimensional reconstruction to examine the complex of the utrophin tandem CH domain with F-actin. In contrast to our previously published study, a closed conformation of the two calponin-homology domains was suggested in the new work. We show here that the new results can be explained by incomplete binding of utrophin to actin, heterogeneity in the mode of binding, and angular disorder in F-actin. We conclude that helical averaging applied to disordered filaments is responsible for their results, and that approaches designed to separate out homogeneous subsets within such filamentous complexes offer many advantages.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, Jordan Hill Box 800773, Charlottesville, VA 22908-0733, USA.
authors.forename: Vitold E
authors.initials: VE
authors.lastname: Galkin
authors.forename: Albina
authors.initials: A
authors.lastname: Orlova
authors.forename: Margaret S
authors.initials: MS
authors.lastname: VanLoock
authors.forename: Edward H
authors.initials: EH
authors.lastname: Egelman
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000648:ultrastructure; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000648:ultrastructure; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000737:chemistry* / Q000648:ultrastructure; D008840:Microfilament Proteins; D008854:Microscopy, Electron; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D049411:Utrophin; D000096985:Calponins
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D049411:Utrophin; D000096985:Calponins