5jlf Citations

Cryo-EM structure of a human cytoplasmic actomyosin complex at near-atomic resolution.

Nature (2016)
Related entries: 5jlh, 3j8a

Cited: 31 times
EuropePMC logo PMID: 27324845


The interaction of myosin with actin filaments is the central feature of muscle contraction and cargo movement along actin filaments of the cytoskeleton. The energy for these movements is generated during a complex mechanochemical reaction cycle. Crystal structures of myosin in different states have provided important structural insights into the myosin motor cycle when myosin is detached from F-actin. The difficulty of obtaining diffracting crystals, however, has prevented structure determination by crystallography of actomyosin complexes. Thus, although structural models exist of F-actin in complex with various myosins, a high-resolution structure of the F-actin-myosin complex is missing. Here, using electron cryomicroscopy, we present the structure of a human rigor actomyosin complex at an average resolution of 3.9 Å. The structure reveals details of the actomyosin interface, which is mainly stabilized by hydrophobic interactions. The negatively charged amino (N) terminus of actin interacts with a conserved basic motif in loop 2 of myosin, promoting cleft closure in myosin. Surprisingly, the overall structure of myosin is similar to rigor-like myosin structures in the absence of F-actin, indicating that F-actin binding induces only minimal conformational changes in myosin. A comparison with pre-powerstroke and intermediate (Pi-release) states of myosin allows us to discuss the general mechanism of myosin binding to F-actin. Our results serve as a strong foundation for the molecular understanding of cytoskeletal diseases, such as autosomal dominant hearing loss and diseases affecting skeletal and cardiac muscles, in particular nemaline myopathy and hypertrophic cardiomyopathy.

Reviews citing this publication (8)

  1. Hypertrophic cardiomyopathy and the myosin mesa: viewing an old disease in a new light. Trivedi DV, Adhikari AS, Sarkar SS, Ruppel KM, Spudich JA. Biophys Rev 10 27-48 (2018)
  2. Classifying Cardiac Actin Mutations Associated With Hypertrophic Cardiomyopathy. Despond EA, Dawson JF. Front Physiol 9 405 (2018)
  3. While the revolution will not be crystallized, biochemistry reigns supreme. Takizawa Y, Binshtein E, Erwin AL, Pyburn TM, Mittendorf KF, Ohi MD. Protein Sci 26 69-81 (2017)
  4. Keeping the focus on biophysics and actin filaments in Nagoya: A report of the 2016 "now in actin" symposium. Fujiwara I, Narita A. Cytoskeleton (Hoboken) 74 450-464 (2017)
  5. Electron Cryo-microscopy as a Tool for Structure-Based Drug Development. Merino F, Raunser S. Angew Chem Int Ed Engl 56 2846-2860 (2017)
  6. Resolution advances in cryo-EM enable application to drug discovery. Subramaniam S, Earl LA, Falconieri V, Milne JL, Egelman EH. Curr Opin Struct Biol 41 194-202 (2016)
  7. How Myosin Generates Force on Actin Filaments. Houdusse A, Sweeney HL. Trends Biochem Sci 41 989-997 (2016)
  8. Structural complexity of filaments formed from the actin and tubulin folds. Jiang S, Ghoshdastider U, Narita A, Popp D, Robinson RC. Commun Integr Biol 9 e1242538 (2016)

Articles citing this publication (23)

  1. The myosin mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations. Nag S, Trivedi DV, Sarkar SS, Adhikari AS, Sunitha MS, Sutton S, Ruppel KM, Spudich JA. Nat Struct Mol Biol 24 525-533 (2017)
  2. High-resolution Single Particle Analysis from Electron Cryo-microscopy Images Using SPHIRE. Moriya T, Saur M, Stabrin M, Merino F, Voicu H, Huang Z, Penczek PA, Raunser S, Gatsogiannis C. J Vis Exp (2017)
  3. Three mammalian tropomyosin isoforms have different regulatory effects on nonmuscle myosin-2B and filamentous β-actin in vitro. Pathan-Chhatbar S, Taft MH, Reindl T, Hundt N, Latham SL, Manstein DJ. J Biol Chem 293 863-875 (2018)
  4. 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)
  5. Molecular mechanisms of deregulation of the thin filament associated with the R167H and K168E substitutions in tropomyosin Tpm1.1. Borovikov YS, Rysev NA, Avrova SV, Karpicheva OE, Borys D, Moraczewska J. Arch Biochem Biophys 614 28-40 (2017)
  6. Advances in Structural Biology and the Application to Biological Filament Systems. Popp D, Koh F, Scipion CPM, Ghoshdastider U, Narita A, Holmes KC, Robinson RC. Bioessays 40 e1700213 (2018)
  7. Cryo-EM structure of the bacterial actin AlfA reveals unique assembly and ATP-binding interactions and the absence of a conserved subdomain. Usluer GD, DiMaio F, Yang SK, Hansen JM, Polka JK, Mullins RD, Kollman JM. Proc Natl Acad Sci U S A 115 3356-3361 (2018)
  8. Cryo-EM structures reveal specialization at the myosin VI-actin interface and a mechanism of force sensitivity. Gurel PS, Kim LY, Ruijgrok PV, Omabegho T, Bryant Z, Alushin GM. Elife 6 (2017)
  9. Simultaneous refinement of inaccurate local regions and overall structure in the CASP12 protein model refinement experiment. Lee GR, Heo L, Seok C. Proteins 86 Suppl 1 168-176 (2018)
  10. Near-atomic structure of jasplakinolide-stabilized malaria parasite F-actin reveals the structural basis of filament instability. Pospich S, Kumpula EP, von der Ecken J, Vahokoski J, Kursula I, Raunser S. Proc Natl Acad Sci U S A 114 10636-10641 (2017)
  11. Tropomyosins. Gunning PW, Hardeman EC. Curr Biol 27 R8-R13 (2017)
  12. Thermodynamic aspects of ATP hydrolysis of actomyosin complex. Zhang XC, Feng W. Biophys Rep 2 87-94 (2016)
  13. `Atomic resolution': a badly abused term in structural biology. Wlodawer A, Dauter Z. Acta Crystallogr D Struct Biol 73 379-380 (2017)
  14. Ca2+-induced movement of tropomyosin on native cardiac thin filaments revealed by cryoelectron microscopy. Risi C, Eisner J, Belknap B, Heeley DH, White HD, Schröder GF, Galkin VE. Proc Natl Acad Sci U S A 114 6782-6787 (2017)
  15. Kinetic adaptation of human Myo19 for active mitochondrial transport to growing filopodia tips. Ušaj M, Henn A. Sci Rep 7 11596 (2017)
  16. Structural basis for high-affinity actin binding revealed by a β-III-spectrin SCA5 missense mutation. Avery AW, Fealey ME, Wang F, Orlova A, Thompson AR, Thomas DD, Hays TS, Egelman EH. Nat Commun 8 1350 (2017)
  17. Steric hindrance in the upper 50 kDa domain of the motor Myo2p leads to cytokinesis defects in fission yeast. Palani S, Srinivasan R, Zambon P, Kamnev A, Gayathri P, Balasubramanian MK. J Cell Sci 131 (2018)
  18. The shaker-1 mouse myosin VIIa deafness mutation results in a severely reduced rate of the ATP hydrolysis step. Xiong A, Haithcock J, Liu Y, Eusner L, McConnell M, White HD, Belknap B, Forgacs E. J Biol Chem 293 819-829 (2018)
  19. Long-range coupling between ATP-binding and lever-arm regions in myosin via dielectric allostery. Sato T, Ohnuki J, Takano M. J Chem Phys 147 215101 (2017)
  20. Mechanistic insights into the active site and allosteric communication pathways in human nonmuscle myosin-2C. Chinthalapudi K, Heissler SM, Preller M, Sellers JR, Manstein DJ. Elife 6 (2017)
  21. Catastrophic disassembly of actin filaments via Mical-mediated oxidation. Grintsevich EE, Ge P, Sawaya MR, Yesilyurt HG, Terman JR, Zhou ZH, Reisler E. Nat Commun 8 2183 (2017)
  22. Interaction of isolated cross-linked short actin oligomers with the skeletal muscle myosin motor domain. Qu Z, Fujita-Becker S, Ballweber E, Ince S, Herrmann C, Schröder RR, Mannherz HG. FEBS J 285 1715-1729 (2018)
  23. Affimer proteins for F-actin: novel affinity reagents that label F-actin in live and fixed cells. Lopata A, Hughes R, Tiede C, Heissler SM, Sellers JR, Knight PJ, Tomlinson D, Peckham M. Sci Rep 8 6572 (2018)

Related citations provided by authors (1)

  1. Structure of the F-actin--tropomyosin complex.. von der Ecken J, Müller M, Lehman W, Manstein DJ, Penczek PA, Raunser S Nature (2014)