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The structural basis of the cross-bridge cycle. DECORATED ACTIN was the first em reconstruction Moore, Huxley, and DeRosier 1970 J. Mol Biol.

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Presentation on theme: "The structural basis of the cross-bridge cycle. DECORATED ACTIN was the first em reconstruction Moore, Huxley, and DeRosier 1970 J. Mol Biol."— Presentation transcript:

1 The structural basis of the cross-bridge cycle

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

3 Reconstruction by filtered least squares

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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!!

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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,

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19 Four sub-domain refinement

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26 The cross-bridge cycle As revealed by crystallography

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

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29 Lymn & Taylor, 1971

30 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?

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36 switch 1

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38 Fischer et al (2005) PNAS

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40 Weak and Strong Binding

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44 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

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46 Rayment_chicken

47 Upper/lower 50K fitted

48 Myo 5

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