5jlf Citations

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

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

Cited: 13 times
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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 (7)

  1. 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)
  2. 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 (2017)
  3. 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) (2017)
  4. Electron Cryo-microscopy as a Tool for Structure-Based Drug Development. Merino F, Raunser S. Angew. Chem. Int. Ed. Engl. 56 2846-2860 (2017)
  5. 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)
  6. How Myosin Generates Force on Actin Filaments. Houdusse A, Sweeney HL. Trends Biochem. Sci. 41 989-997 (2016)
  7. 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 (6)

  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. 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)
  4. Tropomyosins. Gunning PW, Hardeman EC. Curr. Biol. 27 R8-R13 (2017)
  5. Thermodynamic aspects of ATP hydrolysis of actomyosin complex. Zhang XC, Feng W. Biophys Rep 2 87-94 (2016)
  6. Kinetic adaptation of human Myo19 for active mitochondrial transport to growing filopodia tips. Ušaj M, Henn A. Sci Rep 7 11596 (2017)

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)