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-Structure paper
タイトル | Structural basis for tunable control of actin dynamics by myosin-15 in mechanosensory stereocilia. |
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ジャーナル・号・ページ | Sci Adv, Vol. 8, Issue 29, Page eabl4733, Year 2022 |
掲載日 | 2022年7月22日 |
著者 | Rui Gong / Fangfang Jiang / Zane G Moreland / Matthew J Reynolds / Santiago Espinosa de Los Reyes / Pinar Gurel / Arik Shams / James B Heidings / Michael R Bowl / Jonathan E Bird / Gregory M Alushin / |
PubMed 要旨 | The motor protein myosin-15 is necessary for the development and maintenance of mechanosensory stereocilia, and mutations in myosin-15 cause hereditary deafness. In addition to transporting actin ...The motor protein myosin-15 is necessary for the development and maintenance of mechanosensory stereocilia, and mutations in myosin-15 cause hereditary deafness. In addition to transporting actin regulatory machinery to stereocilia tips, myosin-15 directly nucleates actin filament ("F-actin") assembly, which is disrupted by a progressive hearing loss mutation (p.D1647G, ""). Here, we present cryo-electron microscopy structures of myosin-15 bound to F-actin, providing a framework for interpreting the impacts of deafness mutations on motor activity and actin nucleation. Rigor myosin-15 evokes conformational changes in F-actin yet maintains flexibility in actin's D-loop, which mediates inter-subunit contacts, while the mutant locks the D-loop in a single conformation. Adenosine diphosphate-bound myosin-15 also locks the D-loop, which correspondingly blunts actin-polymerization stimulation. We propose myosin-15 enhances polymerization by bridging actin protomers, regulating nucleation efficiency by modulating actin's structural plasticity in a myosin nucleotide state-dependent manner. This tunable regulation of actin polymerization could be harnessed to precisely control stereocilium height. |
リンク | Sci Adv / PubMed:35857845 / PubMed Central |
手法 | EM (らせん対称) / EM (単粒子) |
解像度 | 2.62 - 4.18 Å |
構造データ | EMDB-24321, PDB-7r8v: EMDB-24322, PDB-7r91: EMDB-24399, PDB-7rb8: EMDB-24400, PDB-7rb9: EMDB-26459, PDB-7udt: EMDB-26460, PDB-7udu: EMDB-26461: cryo-EM structure of the ADP state wild type myosin-15-F-actin complex (symmetry expansion) EMDB-26462: cryo-EM structure of the rigor state wild type myosin-15-F-actin complex (symmetry expansion) EMDB-26463: cryo-EM structure of the ADP state actin filament (symmetry expansion) EMDB-26464: Cryo-EM structure of the rigor state Jordan myosin-15-F-actin complex (symmetry expansion) |
化合物 | ChemComp-ADP: ChemComp-MG: |
由来 |
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キーワード | CELL ADHESION / filamentous actin / cytoskeleton / adhesion / contractility / MOTOR PROTEIN / myosin motor proteins / actin cytoskeleton / stereocilia / deafness / MOTOR PROTEIN/ATP Binding Protein / MOTOR PROTEIN-ATP Binding Protein complex |