title: The Arg non-receptor tyrosine kinase modifies F-actin structure.
abstract: The Arg (Abl-related gene) protein belongs to the Abl family of non-receptor tyrosine kinases that regulate cell motility and morphogenesis. It contains two actin-binding domains, one containing the talin-like I/LWEQ motif, and a C-terminal calponin homology (CH) domain. We used electron microscopy and single particle image analysis to reconstruct complexes of F-actin with full-length Arg, and fragments lacking either the I/LWEQ or CH domains. The Arg CH domain binds to actin's subdomain-1 (SD1) and induces a tilt of actin protomers. The I/LWEQ domain binds to either SD1 or SD4, closing the nucleotide binding cleft of actin. Although Arg can use either its CH or ILWEQ domains to bind an actin filament, both domains within Arg cannot bind simultaneously to adjacent protomers in the filament, consistent with its F-actin-bundling activity. The conformational changes in the filament introduced by Arg can explain the cooperative binding of Arg to F-actin and might prevent other actin binding proteins from binding to actin filaments.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, 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: Anthony J
authors.initials: AJ
authors.lastname: Koleske
authors.forename: Edward H
authors.initials: EH
authors.lastname: Egelman
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D007091:Image Processing, Computer-Assisted; D008854:Microscopy, Electron; D008958:Models, Molecular; D010446:Peptide Fragments; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D010446:Peptide Fragments; D021122:Protein Subunits; C426236:ARG tyrosine kinase; D011505:Protein-Tyrosine Kinases