Structural insights into the tropomodulin assembly at the pointed ends of actin filaments
| Autor: | Alla S. Kostyukova, Garry E. Smith, Natalia Moroz, Balaganesh Kuruba, Kyle D. Swain, Trenton J. Williams, Dmitri Tolkatchev, Kaitlin A. Smith |
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| Rok vydání: | 2020 |
| Předmět: |
Gene isoform
0303 health sciences biology Chemistry 030302 biochemistry & molecular biology Articles macromolecular substances Molecular Dynamics Simulation musculoskeletal system Biochemistry Tropomyosin Actin Cytoskeleton Mice 03 medical and health sciences Actin dynamics biology.protein Biophysics Animals Protein Isoforms Actin-binding protein Molecular Biology Tropomodulin Actin 030304 developmental biology |
| Zdroj: | Protein Sci |
| ISSN: | 1469-896X 0961-8368 |
| Popis: | Tropomodulins are a family of important regulators of actin dynamics at the pointed ends of actin filaments. Four isoforms of tropomodulin, Tmod1‐Tmod4, are expressed in vertebrates. Binding of tropomodulin to the pointed end is dependent on tropomyosin, an actin binding protein that itself is represented in mammals by up to 40 isoforms. The understanding of the regulatory role of the tropomodulin/tropomyosin molecular diversity has been limited due to the lack of a three‐dimensional structure of the tropomodulin/tropomyosin complex. In this study, we mapped tropomyosin residues interacting with two tropomyosin‐binding sites of tropomodulin and generated a three‐dimensional model of the tropomodulin/tropomyosin complex for each of these sites. The models were refined by molecular dynamics simulations and validated via building a self‐consistent three‐dimensional model of tropomodulin assembly at the pointed end. The model of the pointed‐end Tmod assembly offers new insights in how Tmod binding ensures tight control over the pointed end dynamics. |
| Databáze: | OpenAIRE |
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