1. The structural basis of the cross-bridge cycle

2. was the first em reconstruction Moore, Huxley, and DeRosier
DECORATED ACTIN
was the first em reconstruction
Moore, Huxley, and DeRosier
1970 J. Mol Biol.

3. Reconstruction by filtered least squares

8. Projection every 1° (181 projections)
Number of observational equations is
161 x 181=29141
Order of normal matrix
Problem should be well determined

9. Oops!!

11. Case 2. Projection every 3°, not enough data to invert the normal matrix. How much data is there?
To determine the rank of a positive (semi) definite matrix we determine its eigenvalue spectrum

12. Decorated actin at 13Å resolving power calculated by filtered least squares

13. Electron cryo-microscopy (of decorated actin) shows how strong binding of myosin to actin releases nucleotide
Holmes, Angert, Kull, Jahn, Schroeder (2003) Nature 425,

19. Four sub-domain refinement

26. The cross-bridge cycle
As revealed by crystallography

27. The molecular mechanism of muscle contraction
Geeves, M.A. & Holmes, K.C. (2005)
The molecular mechanism of muscle contraction
Adv Protein Chem 71,

29. Lymn & Taylor, 1971

30. It must bind to actin strongly or weakly
The myosin motor domain must move the lever arm from pre- to post- power stroke.
It must bind to actin strongly or weakly
Both functions are controlled by ATP binding and hydrolysis

31. Crystallography on the motor
domain (particularly Dictyostelium
Myosin 2) shows two conformations of myosin:
lever UP and lever DOWN

32. Diskussionsthemen
Nennen Sie die Hauptthesen, über die Sie sprechen werden.

33. Thema 1 Details über das Thema Argumente und Beispiele
Warum ist das Thema für Ihr Publikum von Bedeutung?

36. switch 1

38. Fischer et al (2005) PNAS

39. Fischer et al (2005) PNAS

40. Weak and Strong Binding

43. Fig 27

44. Coureux, P. D. Wells, A. L. Menetrey, J. Yengo, C. M. Morris, C. A
Coureux, P. D.Wells, A. L.Menetrey, J.Yengo, C. M.Morris, C. A.Sweeney, H. L.Houdusse, A. (2003)
A structural state of the myosin V motor without bound nucleotide
Nature

46. Rayment_chicken

47. Upper/lower 50K fitted

48. Myo 5

49. ?