NMR solution structures of actin depolymerizing factor homology domains |
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Authors: | Alexander K. Goroncy Seizo Koshiba Naoya Tochio Tadashi Tomizawa Manami Sato Makato Inoue Satoru Watanabe Yoshihide Hayashizaki Akiko Tanaka Takanori Kigawa Shigeyuki Yokoyama |
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Affiliation: | 1. RIKEN Systems and Structural Biology Center, 1‐7‐22 Suehiro‐cho, Tsurumi‐ku, Yokohama, Kanagawa, Japan;2. RIKEN Omics Sciences Center, 1‐7‐22 Suehiro‐cho, Tsurumi‐ku, Yokohama, Kanagawa, Japan;3. Department of Computational Intelligence and Systems Science, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Yokohama, Japan;4. Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan |
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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 β (mouse). We also determined the structures of mouse GMF γ, 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 β and GMF γ contain two additional β‐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 β and GMF γ. |
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Keywords: | actin‐depolymerizing factor homology domain G‐actin binding F‐actin binding structure stabilization |
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