title: Coronin-1A stabilizes F-actin by bridging adjacent actin protomers and stapling opposite strands of the actin filament.
abstract: Coronins are F-actin-binding proteins that are involved, in concert with Arp2/3, Aip1, and ADF/cofilin, in rearrangements of the actin cytoskeleton. An understanding of coronin function has been hampered by the absence of any structural data on its interaction with actin. Using electron microscopy and three-dimensional reconstruction, we show that coronin-1A binds to three protomers in F-actin simultaneously: it bridges subdomain 1 and subdomain 2 of two adjacent actin subunits along the same long-pitch strand, and it staples subdomain 1 and subdomain 4 of two actin protomers on different strands. Such a mode of binding explains how coronin can stabilize actin filaments in vitro. In addition, we show which residues of F-actin may participate in the interaction with coronin-1A. Human nebulin and Xin, as well as Salmonella invasion protein A, use a similar mechanism to stabilize actin filaments. We suggest that the stapling of subdomain 1 and subdomain 4 of two actin protomers on different strands is a common mechanism for F-actin stabilization utilized by many actin-binding proteins that have no homology.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia, Box 800733, Charlottesville, VA 22908-0733, USA. galkin@virginia.edu
authors.forename: Vitold E
authors.initials: VE
authors.lastname: Galkin
authors.forename: Albina
authors.initials: A
authors.lastname: Orlova
authors.forename: William
authors.initials: W
authors.lastname: Brieher
authors.forename: Hao Yuan
authors.initials: HY
authors.lastname: Kueh
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mitchison
authors.forename: Edward H
authors.initials: EH
authors.lastname: Egelman
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009124:Muscle Proteins; D025941:Protein Interaction Mapping
chemical_list: D000199:Actins; D008840:Microfilament Proteins; D009124:Muscle Proteins; C035620:nebulin; C072061:coronin proteins