Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity

Nature Communications

Volumn 6, Issue , 2015, Pages

  Winkelmann, Donald A ^a   Forgacs, Eva ^b   Miller, Matthew T ^c   Stock, Ann M ^a,c  

^a RUTGERS ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

^b EASTERN VIRGINIA MEDICAL SCHOOL   (United States)

^c RUTGERS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HYBRID PROTEIN; MYOSIN HEAVY CHAIN BETA; MYOSIN II; OMECAMTIV MECARBIL; CARDIAC MYOSIN; GREEN FLUORESCENT PROTEIN; UREA;

CARDIOLOGY; CARDIOVASCULAR DISEASE; DRUG; HYDROLYSIS; PHOSPHATE; PROTEIN;

ACTIN FILAMENT; ALLOSTERISM; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BETA SHEET; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG BINDING SITE; DRUG CONFORMATION; DRUG MECHANISM; HUMAN; HUMAN TISSUE; HYDROLYSIS; MOLECULAR INTERACTION; MOTOR ACTIVITY; MOUSE; NONHUMAN; POLYACRYLAMIDE GEL ELECTROPHORESIS; SKELETAL MUSCLE; TANDEM MASS SPECTROMETRY; ANALOGS AND DERIVATIVES; ANIMAL; BINDING SITE; CELL LINE; CHEMISTRY; DRUG EFFECTS; PROTEIN TERTIARY STRUCTURE;

ALLOSTERIC REGULATION; ALLOSTERIC SITE; ANIMALS; CARDIAC MYOSINS; CELL LINE; GREEN FLUORESCENT PROTEINS; HUMANS; MICE; PROTEIN STRUCTURE, TERTIARY; UREA;

EID: 84938889151     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms8974     Document Type: Article

References (64)

1. Lloyd-Jones, D. et al. Executive summary: heart disease and stroke statistics-2010 update: a report from the American Heart Association. Circulation 121, 948-954 (2010).
2. Teerlink, J. R. A novel approach to improve cardiac performance: cardiac myosin activators. Heart Fail. Rev. 14, 289-298 (2009).
3. Morgan, B. P. et al. Discovery of omecamtiv mecarbil the first, selective, small molecule activator of cardiac Myosin. ACS Med. Chem. Lett. 1, 472-477 (2010).
4. Malik, F. I. et al. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science 331, 1439-1443 (2011).
5. Shen, Y. T. et al. Improvement of cardiac function by a cardiac Myosin activator in conscious dogs with systolic heart failure. Circ. Heart Fail. 3, 522-527 (2010).
6. Liu, Y., White, H. D., Belknap, B., Winkelmann, D. A. & Forgacs, E. Omecamtiv Mecarbil modulates the kinetic and motile properties of porcine beta-cardiac myosin. Biochemistry 54, 1963-1975 (2015).
7. Siemankowski, R. F., Wiseman, M. O. & White, H. D. ADP dissociation from actomyosin subfragment 1 is sufficiently slow to limit the unloaded shortening velocity in vertebrate muscle. Proc. Natl Acad. Sci. USA 82, 658-662 (1985).
8. Wang, Y., Ajtai, K. & Burghardt, T. P. Analytical comparison of natural and pharmaceutical ventricular myosin activators. Biochemistry 53, 5298-5306 (2014).
9. Chow, D., Srikakulam, R., Chen, Y. & Winkelmann, D. A. Folding of the striated muscle myosin motor domain. J. Biol. Chem. 277, 36799-36807 (2002).
10. Liu, L., Srikakulam, R. & Winkelmann, D. A. Unc45 activates Hsp90-dependent folding of the myosin motor domain. J. Biol. Chem. 283, 13185-13193 (2008).
11. Srikakulam, R. & Winkelmann, D. A. Chaperone-mediated folding and assembly of myosin in striated muscle. J. Cell Sci. 117, 641-652 (2004).
12. Wang, Q., Moncman, C. L. & Winkelmann, D. A. Mutations in the motor domain modulate myosin activity and myofibril organization. J. Cell Sci. 116, 4227-4238 (2003).
13. Coureux, P. D., Sweeney, H. L. & Houdusse, A. Three myosin V structures delineate essential features of chemo-mechanical transduction. EMBO J. 23, 4527-4537 (2004).
14. Klenchin, V., Deacon, J., Combs, A., Leinwand, L. & Rayment, I. Cardiac human myosin S1dc, beta isofrom complexed with Mn-AMPPNP. PDB ID: 4DB1. 10.2210/pdb4db1/pdb (2012).
15. Rayment, I. et al. Three-dimensional structure of myosin subfragment-1: a molecular motor. Science 261, 50-58 (1993).
16. Risal, D., Gourinath, S., Himmel, D. M., Szent-Gyorgyi, A. G. & Cohen, C. Myosin subfragment 1 structures reveal a partially bound nucleotide and a complex salt bridge that helps couple nucleotide and actin binding. Proc. Natl Acad. Sci. USA 101, 8930-8935 (2004).
17. Dominguez, R., Freyzon, Y., Trybus, K. M. & Cohen, C. Crystal structure of a vertebrate smooth muscle myosin motor domain and its complex with the essential light chain: visualization of the pre-power stroke state. Cell 94, 559-571 (1998).
18. Houdusse, A., Kalabokis, V. N., Himmel, D., Szent-Gyorgyi, A. G. & Cohen, C. Atomic structure of scallop myosin subfragment S1 complexed with MgADP: a novel conformation of the myosin head. Cell 97, 459-470 (1999).
19. Krissinel, E. & Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774-797 (2007).
20. Behrmann, E. et al. Structure of the rigor actin-tropomyosin-myosin complex. Cell 150, 327-338 (2012).
21. Allingham, J. S., Smith, R. & Rayment, I. The structural basis of blebbistatin inhibition and specificity for myosin II. Nat. Struct. Mol. Biol. 12, 378-379 (2005).
22. Kovacs, M., Toth, J., Hetenyi, C., Malnasi-Csizmadia, A. & Sellers, J. R. Mechanism of blebbistatin inhibition of myosin II. J. Biol. Chem. 279, 35557-35563 (2004).
23. Fedorov, R. et al. The mechanism of pentabromopseudilin inhibition of myosin motor activity. Nat. Struct. Mol. Biol. 16, 80-88 (2009).
24. Preller, M., Chinthalapudi, K., Martin, R., Knolker, H. J. & Manstein, D. J. Inhibition of Myosin ATPase activity by halogenated pseudilins: a structureactivity study. J. Med. Chem. 54, 3675-3685 (2011).
25. Radke, M. B. et al. Small molecule-mediated refolding and activation of myosin motor function. Elife 3, e01603 (2014).
26. Sweeney, H. L. & Houdusse, A. Structural and functional insights into the Myosin motor mechanism. Annu. Rev. Biophys. 39, 539-557 (2010).
27. Changeux, J. P. 50 years of allosteric interactions: the twists and turns of the models. Nat. Rev. Mol. Cell Biol. 14, 819-829 (2013).
28. Greenberg, M. J., Shuman, H. & Ostap, E. M. Inherent force-dependent properties of beta-cardiac myosin contribute to the force-velocity relationship of cardiac muscle. Biophys. J. 107, L41-L44 (2014).
29. Spudich, J. A. Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases. Biophys. J. 106, 1236-1249 (2014).
30. Sun, Y. B., Lou, F. & Irving, M. Calcium-And myosin-dependent changes in troponin structure during activation of heart muscle. J. Physiol. 587, 155-163 (2009).
31. Gourinath, S. et al. Crystal structure of scallop myosin S1 in the pre-power stroke state to 2.6 a resolution: flexibility and function in the head. Structure 11, 1621-1627 (2003).
32. Gulick, A. M., Bauer, C. B., Thoden, J. B. & Rayment, I. X-ray structures of the MgADP, MgATPgammaS, and MgAMPPNP complexes of the Dictyostelium discoideum myosin motor domain. Biochemistry 36, 11619-11628 (1997).
33. Baumketner, A. The mechanism of the converter domain rotation in the recovery stroke of myosin motor protein. Proteins 80, 2701-2710 (2012).
34. Fischer, S., Windshugel, B., Horak, D., Holmes, K. C. & Smith, J. C. Structural mechanism of the recovery stroke in the myosin molecular motor. Proc. Natl Acad. Sci. USA 102, 6873-6878 (2005).
35. Furch, M., Fujita-Becker, S., Geeves, M. A., Holmes, K. C. & Manstein, D. J. Role of the salt-bridge between switch-1 and switch-2 of Dictyostelium myosin. J. Mol. Biol. 290, 797-809 (1999).
36. Kintses, B., Yang, Z. & Malnasi-Csizmadia, A. Experimental investigation of the seesaw mechanism of the relay region that moves the myosin lever arm. J. Biol. Chem. 283, 34121-34128 (2008).
37. Koppole, S., Smith, J. C. & Fischer, S. The structural coupling between ATPase activation and recovery stroke in the myosin II motor. Structure 15, 825-837 (2007).
38. Malnasi-Csizmadia, A. et al. Kinetic resolution of a conformational transition and the ATP hydrolysis step using relaxation methods with a Dictyostelium myosin II mutant containing a single tryptophan residue. Biochemistry 40, 12727-12737 (2001).
39. Sweeney, H. L. & Houdusse, A. The motor mechanism of myosin V: insights for muscle contraction. Philos. Trans. R Soc. Lond. B Biol. Sci. 359, 1829-1841 (2004).
40. Arad, M. et al. Gene mutations in apical hypertrophic cardiomyopathy. Circulation 112, 2805-2811 (2005).
41. Sakthivel, S., Joseph, P. K., Tharakan, J. M., Vosberg, H. P. & Rajamanickam, C. A novel missense mutation (R712L) adjacent to the 'active thiol' region of the cardiac beta-myosin heavy chain gene causing hypertrophic cardiomyopathy in an Indian family. Hum. Mutat. 15, 298-299 (2000).
42. Holmes, K. C., Schroder, R. R., Sweeney, H. L. & Houdusse, A. The structure of the rigor complex and its implications for the power stroke. Philos. Trans. R Soc. Lond. B Biol. Sci. 359, 1819-1828 (2004).
43. Roosild, T. P., Castronovo, S. & Choe, S. Structure of anti-FLAG M2 Fab domain and its use in the stabilization of engineered membrane proteins. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 62, 835-839 (2006).
44. He, T. C. et al. A simplified system for generating recombinant adenoviruses. Proc. Natl Acad. Sci. USA 95, 2509-2514 (1998).
45. Kinose, F., Wang, S. X., Kidambi, U. S., Moncman, C. L. & Winkelmann, D. A. Glycine 699 is pivotal for the motor activity of skeletal muscle myosin. J. Cell Biol. 134, 895-909 (1996).
46. Barua, B., Winkelmann, D. A., White, H. D. & Hitchcock-DeGregori, S. E. Regulation of actin-myosin interaction by conserved periodic sites of tropomyosin. Proc. Natl Acad. Sci. USA 109, 18425-18430 (2012).
47. Winkelmann, D. A., Bourdieu, L., Ott, A., Kinose, F. & Libchaber, A. Flexibility of myosin attachment to surfaces influences F-Actin motion. Biophys. J. 68, 2444-2453 (1995).
48. Bourdieu, L., Magnasco, M. O., Winkelmann, D. A. & Libchaber, A. Actin filaments on myosin beds: The velocity distribution. Phys. Rev. E 52, 6573-6579 (1995).
49. Forgacs, E. et al. Switch 1 mutation S217A converts myosin V into a low duty ratio motor. J. Biol. Chem. 284, 2138-2149 (2009).
50. Potterton, E., Briggs, P., Turkenburg, M. & Dodson, E. A graphical user interface to the CCP4 program suite. Acta Crystallogr. D Biol. Crystallogr. 59, 1131-1137 (2003).
51. Evans, P. R. & Murshudov, G. N. How good are my data and what is the resolution? Acta Crystallogr. D Biol. Crystallogr. 69, 1204-1214 (2013).
52. Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221 (2010).
53. Shu, X. et al. An alternative excited-state proton transfer pathway in green fluorescent protein variant S205V. Protein Sci. 16, 2703-2710 (2007).
54. Terwilliger, T. C. et al. Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard. Acta Crystallogr. D Biol. Crystallogr. 64, 61-69 (2008).
55. Afonine, P. V. et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. D Biol. Crystallogr. 68, 352-367 (2012).
56. Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486-501 (2010).
57. Berman, H. M. et al. The Protein Data Bank. Nucleic Acids Res. 28, 235-242 (2000).
58. Chen, V. B. et al. MolProbity: all-Atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 12-21 (2010).
59. Terwilliger, T. C., Klei, H., Adams, P. D., Moriarty, N. W. & Cohn, J. D. Automated ligand fitting by core-fragment fitting and extension into density. Acta Crystallogr. D Biol. Crystallogr. 62, 915-922 (2006).
60. Moriarty, N. W., Grosse-Kunstleve, R. W. & Adams, P. D. electronic Ligand Builder and Optimization Workbench (eLBOW): a tool for ligand coordinate and restraint generation. Acta Crystallogr. D Biol. Crystallogr. 65, 1074-1080 (2009).
61. Karplus, P. A. & Diederichs, K. Linking crystallographic model and data quality. Science 336, 1030-1033 (2012).
62. Diederichs, K. & Karplus, P. A. Better models by discarding data? Acta Crystallogr. D Biol. Crystallogr. 69, 1215-1222 (2013).
63. Wang, J. & Wing, R. A. Diamonds in the rough: a strong case for the inclusion of weak-intensity X-ray diffraction data. Acta Crystallogr. D Biol. Crystallogr. 70, 1491-1497 (2014).
64. Laskowski, R. A. & Swindells, M. B. LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. J. Chem. Inf. Model 51, 2778-2786 (2011).