EMD-26459
cryo-EM structure of the rigor state wild type myosin-15-F-actin complex (symmetry expansion and re-centering)
EMD-26459
Single-particle3.17 Å
Deposition: 20/03/2022Map released: 03/08/2022
Last modified: 03/08/2022
Sample Organism:
chicken,
Mus musculus
Sample: the rigor state wild type myosin-15-F-actin complex
Fitted models: 7udt (Avg. Q-score: 0.431)
Raw data: EMPIAR-11143
Deposition Authors: Gong R
,
Reynolds MJ ,
Alushin GM
Sample: the rigor state wild type myosin-15-F-actin complex
Fitted models: 7udt (Avg. Q-score: 0.431)
Raw data: EMPIAR-11143
Deposition Authors: Gong R
,
Reynolds MJ ,
Alushin GM
Structural basis for tunable control of actin dynamics by myosin-15 in mechanosensory stereocilia.
Gong R ,
Jiang F ,
Moreland ZG ,
Reynolds MJ ,
de Los Reyes SE ,
Gurel P,
Shams A ,
Heidings JB ,
Bowl MR ,
Bird JE ,
Alushin GM
(2022) Sci Adv , 8 , eabl4733 - eabl4733
,
Jiang F ,
Moreland ZG ,
Reynolds MJ ,
de Los Reyes SE ,
Gurel P,
Shams A ,
Heidings JB ,
Bowl MR ,
Bird JE ,
Alushin GM
(2022) Sci Adv , 8 , eabl4733 - eabl4733
Abstract:
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, "jordan"). 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 jordan 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.
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, "jordan"). 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 jordan 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.