title: NMR solution structures of actin depolymerizing factor homology domains.
abstract: Actin is one of the most conserved proteins in nature. Its assembly and disassembly are regulated by many proteins, including the family of actin-depolymerizing factor homology (ADF-H) domains. ADF-H domains can be divided into five classes: ADF/cofilin, glia maturation factor (GMF), coactosin, twinfilin, and Abp1/drebrin. The best-characterized class is ADF/cofilin. The other four classes have drawn much less attention and very few structures have been reported. This study presents the solution NMR structure of the ADF-H domain of human HIP-55-drebrin-like protein, the first published structure of a drebrin-like domain (mammalian), and the first published structure of GMF beta (mouse). We also determined the structures of mouse GMF gamma, the mouse coactosin-like domain and the C-terminal ADF-H domain of mouse twinfilin 1. Although the overall fold of the five domains is similar, some significant differences provide valuable insights into filamentous actin (F-actin) and globular actin (G-actin) binding, including the identification of binding residues on the long central helix. This long helix is stabilized by three or four residues. Notably, the F-actin binding sites of mouse GMF beta and GMF gamma contain two additional beta-strands not seen in other ADF-H structures. The G-actin binding site of the ADF-H domain of human HIP-55-drebrin-like protein is absent and distorted in mouse GMF beta and GMF gamma.
authors.affiliation: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Goroncy
authors.forename: Seizo
authors.initials: S
authors.lastname: Koshiba
authors.forename: Naoya
authors.initials: N
authors.lastname: Tochio
authors.forename: Tadashi
authors.initials: T
authors.lastname: Tomizawa
authors.forename: Manami
authors.initials: M
authors.lastname: Sato
authors.forename: Makato
authors.initials: M
authors.lastname: Inoue
authors.forename: Satoru
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanaka
authors.forename: Takanori
authors.initials: T
authors.lastname: Kigawa
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D051339:Actin Depolymerizing Factors / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics*; D020904:Glia Maturation Factor / Q000737:chemistry / Q000235:genetics; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010802:Phylogeny; D011485:Protein Binding; D055550:Protein Stability; D017434:Protein Structure, Tertiary / Q000235:genetics*; D016415:Sequence Alignment; D040681:Structural Homology, Protein
chemical_list: D051339:Actin Depolymerizing Factors; D020904:Glia Maturation Factor; D008840:Microfilament Proteins; C485551:Cotl1 protein, mouse; C485190:Twf1 protein, mouse