6c1d › Citations

High-resolution cryo-EM structures of actin-bound myosin states reveal the mechanism of myosin force sensing.

Mentes A, Huehn A, Liu X, Zwolak A, Dominguez R, Shuman H, Ostap EM, Sindelar CV
Proc Natl Acad Sci U S A 115 1292-1297 (2018)
Related entries: 5v7x, 6c1g, 6c1h

Cited: 64 times
EuropePMC logo PMID: 29358376

Abstract

Myosins adjust their power outputs in response to mechanical loads in an isoform-dependent manner, resulting in their ability to dynamically adapt to a range of motile challenges. Here, we reveal the structural basis for force-sensing based on near-atomic resolution structures of one rigor and two ADP-bound states of myosin-IB (myo1b) bound to actin, determined by cryo-electron microscopy. The two ADP-bound states are separated by a 25° rotation of the lever. The lever of the first ADP state is rotated toward the pointed end of the actin filament and forms a previously unidentified interface with the N-terminal subdomain, which constitutes the upper half of the nucleotide-binding cleft. This pointed-end orientation of the lever blocks ADP release by preventing the N-terminal subdomain from the pivoting required to open the nucleotide binding site, thus revealing how myo1b is inhibited by mechanical loads that restrain lever rotation. The lever of the second ADP state adopts a rigor-like orientation, stabilized by class-specific elements of myo1b. We identify a role for this conformation as an intermediate in the ADP release pathway. Moreover, comparison of our structures with other myosins reveals structural diversity in the actomyosin binding site, and we reveal the high-resolution structure of actin-bound phalloidin, a potent stabilizer of filamentous actin. These results provide a framework to understand the spectrum of force-sensing capacities among the myosin superfamily.

Reviews - 6c1d mentioned but not cited (1)

  1. Towards a structural understanding of the remodeling of the actin cytoskeleton. Merino F, Pospich S, Raunser S. Semin Cell Dev Biol 102 51-64 (2020)

Articles - 6c1d mentioned but not cited (10)

  1. High-resolution cryo-EM structures of actin-bound myosin states reveal the mechanism of myosin force sensing. Mentes A, Huehn A, Liu X, Zwolak A, Dominguez R, Shuman H, Ostap EM, Sindelar CV. Proc Natl Acad Sci U S A 115 1292-1297 (2018)
  2. High-resolution structures of the actomyosin-V complex in three nucleotide states provide insights into the force generation mechanism. Pospich S, Sweeney HL, Houdusse A, Raunser S. Elife 10 e73724 (2021)
  3. Alternative N-terminal regions of Drosophila myosin heavy chain II regulate communication of the purine binding loop with the essential light chain. Bloemink MJ, Hsu KH, Geeves MA, Bernstein SI. J Biol Chem 295 14522-14535 (2020)
  4. Cryo-electron microscopy structures of pyrene-labeled ADP-Pi- and ADP-actin filaments. Chou SZ, Pollard TD. Nat Commun 11 5897 (2020)
  5. Structural insights into actin filament recognition by commonly used cellular actin markers. Kumari A, Kesarwani S, Javoor MG, Vinothkumar KR, Sirajuddin M. EMBO J 39 e104006 (2020)
  6. Structural basis of the filamin A actin-binding domain interaction with F-actin. Iwamoto DV, Huehn A, Simon B, Huet-Calderwood C, Baldassarre M, Sindelar CV, Calderwood DA. Nat. Struct. Mol. Biol. 25 918-927 (2018)
  7. Actomyosin Complex. Pepper I, Galkin VE. Subcell Biochem 99 421-470 (2022)
  8. Atomistic Models from Orientation and Distance Constraints Using EPR of a Bifunctional Spin Label. Binder BP, Thompson AR, Thomas DD. Biophys J 117 319-330 (2019)
  9. High-resolution structures of malaria parasite actomyosin and actin filaments. Vahokoski J, Calder LJ, Lopez AJ, Molloy JE, Kursula I, Rosenthal PB. PLoS Pathog 18 e1010408 (2022)
  10. Integrating comparative modeling and accelerated simulations reveals conformational and energetic basis of actomyosin force generation. Ma W, You S, Regnier M, McCammon JA. Proc Natl Acad Sci U S A 120 e2215836120 (2023)


Reviews citing this publication (9)

  1. Effects of forces on chromatin. Amar K, Wei F, Chen J, Wang N. APL Bioeng 5 041503 (2021)
  2. Classifying Cardiac Actin Mutations Associated With Hypertrophic Cardiomyopathy. Despond EA, Dawson JF. Front Physiol 9 405 (2018)
  3. Polymerization and depolymerization of actin with nucleotide states at filament ends. Fujiwara I, Takeda S, Oda T, Honda H, Narita A, Maéda Y. Biophys Rev 10 1513-1519 (2018)
  4. Striated muscle proteins are regulated both by mechanical deformation and by chemical post-translational modification. Solís C, Russell B. Biophys Rev 13 679-695 (2021)
  5. Synthetic biology approaches to dissecting linear motor protein function: towards the design and synthesis of artificial autonomous protein walkers. Linke H, Höcker B, Furuta K, Forde NR, Curmi PMG. Biophys Rev 12 1041-1054 (2020)
  6. Actin polymerization and depolymerization in developing vertebrates. Bai Y, Zhao F, Wu T, Chen F, Pang X. Front Physiol 14 1213668 (2023)
  7. Class I myosins: Highly versatile proteins with specific functions in the immune system. Girón-Pérez DA, Piedra-Quintero ZL, Santos-Argumedo L. J Leukoc Biol 105 973-981 (2019)
  8. Does the Actin Network Architecture Leverage Myosin-I Functions? Pernier J, Schauer K. Biology (Basel) 11 989 (2022)
  9. The Central Role of the F-Actin Surface in Myosin Force Generation. Doran MH, Lehman W. Biology (Basel) 10 1221 (2021)

Articles citing this publication (44)

  1. Structure of the Lifeact-F-actin complex. Belyy A, Merino F, Sitsel O, Raunser S. PLoS Biol 18 e3000925 (2020)
  2. The molecular basis for sarcomere organization in vertebrate skeletal muscle. Wang Z, Grange M, Wagner T, Kho AL, Gautel M, Raunser S. Cell 184 2135-2150.e13 (2021)
  3. Structural transitions of F-actin upon ATP hydrolysis at near-atomic resolution revealed by cryo-EM. Merino F, Pospich S, Funk J, Wagner T, Küllmer F, Arndt HD, Bieling P, Raunser S. Nat. Struct. Mol. Biol. 25 528-537 (2018)
  4. Cryo-EM Structure of Actin Filaments from Zea mays Pollen. Ren Z, Zhang Y, Zhang Y, He Y, Du P, Wang Z, Sun F, Ren H. Plant Cell 31 2855-2867 (2019)
  5. Structural basis of actin filament assembly and aging. Oosterheert W, Klink BU, Belyy A, Pospich S, Raunser S. Nature 611 374-379 (2022)
  6. Structures of cofilin-induced structural changes reveal local and asymmetric perturbations of actin filaments. Huehn AR, Bibeau JP, Schramm AC, Cao W, De La Cruz EM, Sindelar CV. Proc Natl Acad Sci U S A 117 1478-1484 (2020)
  7. Myosin with hypertrophic cardiac mutation R712L has a decreased working stroke which is rescued by omecamtiv mecarbil. Snoberger A, Barua B, Atherton JL, Shuman H, Forgacs E, Goldman YE, Winkelmann DA, Ostap EM. Elife 10 e63691 (2021)
  8. Mitotic Spindle Positioning (MISP) is an actin bundler that selectively stabilizes the rootlets of epithelial microvilli. Morales EA, Arnaiz C, Krystofiak ES, Zanic M, Tyska MJ. Cell Rep 39 110692 (2022)
  9. The actin filament twist changes abruptly at boundaries between bare and cofilin-decorated segments. Huehn A, Cao W, Elam WA, Liu X, De La Cruz EM, Sindelar CV. J. Biol. Chem. 293 5377-5383 (2018)
  10. The actomyosin interface contains an evolutionary conserved core and an ancillary interface involved in specificity. Robert-Paganin J, Xu XP, Swift MF, Auguin D, Robblee JP, Lu H, Fagnant PM, Krementsova EB, Trybus KM, Houdusse A, Volkmann N, Hanein D. Nat Commun 12 1892 (2021)
  11. D-loop Dynamics and Near-Atomic-Resolution Cryo-EM Structure of Phalloidin-Bound F-Actin. Das S, Ge P, Oztug Durer ZA, Grintsevich EE, Zhou ZH, Reisler E. Structure 28 586-593.e3 (2020)
  12. Mechanism of actin polymerization revealed by cryo-EM structures of actin filaments with three different bound nucleotides. Chou SZ, Pollard TD. Proc. Natl. Acad. Sci. U.S.A. 116 4265-4274 (2019)
  13. The ATPase mechanism of myosin 15, the molecular motor mutated in DFNB3 human deafness. Jiang F, Takagi Y, Shams A, Heissler SM, Friedman TB, Sellers JR, Bird JE. J Biol Chem 296 100243 (2021)
  14. A reverse stroke characterizes the force generation of cardiac myofilaments, leading to an understanding of heart function. Hwang Y, Washio T, Hisada T, Higuchi H, Kaya M. Proc Natl Acad Sci U S A 118 e2011659118 (2021)
  15. Converter domain mutations in myosin alter structural kinetics and motor function. Gunther LK, Rohde JA, Tang W, Walton SD, Unrath WC, Trivedi DV, Muretta JM, Thomas DD, Yengo CM. J Biol Chem 294 1554-1567 (2019)
  16. Myosin-VIIa is expressed in multiple isoforms and essential for tensioning the hair cell mechanotransduction complex. Li S, Mecca A, Kim J, Caprara GA, Wagner EL, Du TT, Petrov L, Xu W, Cui R, Rebustini IT, Kachar B, Peng AW, Shin JB. Nat Commun 11 2066 (2020)
  17. 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. Sci Adv 8 eabl4733 (2022)
  18. Affimers and nanobodies as molecular probes and their applications in imaging. Cordell P, Carrington G, Curd A, Parker F, Tomlinson D, Peckham M. J Cell Sci 135 jcs259168 (2022)
  19. Conformational distributions of isolated myosin motor domains encode their mechanochemical properties. Porter JR, Meller A, Zimmerman MI, Greenberg MJ, Bowman GR. Elife 9 (2020)
  20. Full-length Plasmodium falciparum myosin A and essential light chain PfELC structures provide new anti-malarial targets. Moussaoui D, Robblee JP, Auguin D, Krementsova EB, Haase S, Blake TCA, Baum J, Robert-Paganin J, Trybus KM, Houdusse A. Elife 9 (2020)
  21. Structural and mechanistic insights into the function of the unconventional class XIV myosin MyoA from Toxoplasma gondii. Powell CJ, Ramaswamy R, Kelsen A, Hamelin DJ, Warshaw DM, Bosch J, Burke JE, Ward GE, Boulanger MJ. Proc. Natl. Acad. Sci. U.S.A. 115 E10548-E10555 (2018)
  22. Cardiomyopathy mutations impact the actin-activated power stroke of human cardiac myosin. Tang W, Ge J, Unrath WC, Desetty R, Yengo CM. Biophys J 120 2222-2236 (2021)
  23. Dynamic and asymmetric fluctuations in the microtubule wall captured by high-resolution cryoelectron microscopy. Debs GE, Cha M, Liu X, Huehn AR, Sindelar CV. Proc Natl Acad Sci U S A 117 16976-16984 (2020)
  24. Molecular regulatory mechanism of human myosin-7a. Holló A, Billington N, Takagi Y, Kengyel A, Sellers JR, Liu R. J Biol Chem 299 105243 (2023)
  25. Plasmodium myosin A drives parasite invasion by an atypical force generating mechanism. Robert-Paganin J, Robblee JP, Auguin D, Blake TCA, Bookwalter CS, Krementsova EB, Moussaoui D, Previs MJ, Jousset G, Baum J, Trybus KM, Houdusse A. Nat Commun 10 3286 (2019)
  26. Structural and Computational Insights into a Blebbistatin-Bound Myosin•ADP Complex with Characteristics of an ADP-Release Conformation along the Two-Step Myosin Power Stoke. Ewert W, Franz P, Tsiavaliaris G, Preller M. Int J Mol Sci 21 E7417 (2020)
  27. A simple and rapid preparation of smooth muscle myosin 2 for the electron microscopic analysis. Bharda AV, Jung HS. Appl Microsc 54 1 (2024)
  28. Actin stabilizing compounds show specific biological effects due to their binding mode. Wang S, Crevenna AH, Ugur I, Marion A, Antes I, Kazmaier U, Hoyer M, Lamb DC, Gegenfurtner F, Kliesmete Z, Ziegenhain C, Enard W, Vollmar A, Zahler S. Sci Rep 9 9731 (2019)
  29. Actin's N-terminal acetyltransferase uncovered. Arnesen T, Marmorstein R, Dominguez R. Cytoskeleton (Hoboken) 75 318-322 (2018)
  30. After the revolution: how is Cryo-EM contributing to muscle research? Bradshaw M, Paul DM. J. Muscle Res. Cell. Motil. 40 93-98 (2019)
  31. Atomic view into Plasmodium actin polymerization, ATP hydrolysis, and fragmentation. Kumpula EP, Lopez AJ, Tajedin L, Han H, Kursula I. PLoS Biol. 17 e3000315 (2019)
  32. Conformational changes linked to ADP release from human cardiac myosin bound to actin-tropomyosin. Doran MH, Rynkiewicz MJ, Rasicci D, Bodt SML, Barry ME, Bullitt E, Yengo CM, Moore JR, Lehman W. J Gen Physiol 155 e202213267 (2023)
  33. Cryo-Electron Microscopy Reveals Cardiac Myosin Binding Protein-C M-Domain Interactions with the Thin Filament. Risi CM, Villanueva E, Belknap B, Sadler RL, Harris SP, White HD, Galkin VE. J Mol Biol 434 167879 (2022)
  34. Double-headed binding of myosin II to F-actin shows the effect of strain on head structure. Hojjatian A, Taylor DW, Daneshparvar N, Fagnant PM, Trybus KM, Taylor KA. J Struct Biol 215 107995 (2023)
  35. Ensembles of human myosin-19 bound to calmodulin and regulatory light chain RLC12B drive multimicron transport. Pollard LW, Coscia SM, Rebowski G, Palmer NJ, Holzbaur ELF, Dominguez R, Ostap EM. J Biol Chem 299 102906 (2023)
  36. Exploiting nanobodies and Affimers for superresolution imaging in light microscopy. Carrington G, Tomlinson D, Peckham M. Mol. Biol. Cell 30 2737-2740 (2019)
  37. High-Resolution Cryo-EM Structure of the Cardiac Actomyosin Complex. Risi C, Schäfer LU, Belknap B, Pepper I, White HD, Schröder GF, Galkin VE. Structure 29 50-60.e4 (2021)
  38. Mechanochemical properties of human myosin-1C are modulated by isoform-specific differences in the N-terminal extension. Giese S, Reindl T, Reinke PYA, Zattelman L, Fedorov R, Henn A, Taft MH, Manstein DJ. J Biol Chem 296 100128 (2021)
  39. Myosin 1b flattens and prunes branched actin filaments. Pernier J, Morchain A, Caorsi V, Bertin A, Bousquet H, Bassereau P, Coudrier E. J Cell Sci 133 jcs247403 (2020)
  40. Nucleotide-dependent conformational changes in the actin filament: Subtler than expected. Dominguez R. Proc. Natl. Acad. Sci. U.S.A. 116 3959-3961 (2019)
  41. Structural basis for power stroke vs. Brownian ratchet mechanisms of motor proteins. Hwang W, Karplus M. Proc. Natl. Acad. Sci. U.S.A. 116 19777-19785 (2019)
  42. Structural insights into actin isoforms. Arora AS, Huang HL, Singh R, Narui Y, Suchenko A, Hatano T, Heissler SM, Balasubramanian MK, Chinthalapudi K. Elife 12 e82015 (2023)
  43. TORC2-Gad8-dependent myosin phosphorylation modulates regulation by calcium. Baker K, Gyamfi IA, Mashanov GI, Molloy JE, Geeves MA, Mulvihill DP. Elife 8 (2019)
  44. Targeting and extending the eukaryotic druggable genome with natural products: cytoskeletal targets of natural products. Risinger AL, Du L. Nat Prod Rep 37 634-652 (2020)


Quick links