How actin initiates the motor activity of Myosin.
Fundamental to cellular processes are directional movements driven by molecular motors. A common theme for these and other molecular machines driven by ATP is that controlled release of hydrolysis products is essential for using the chemical energy efficiently. Mechanochemical transduction by myosin motors on actin is coupled to unknown structural changes that result in the sequential release of inorganic phosphate (Pi) and MgADP. We present here a myosin structure possessing an actin-binding interface and a tunnel (back door) that creates an escape route for Pi with a minimal rotation of the myosin lever arm that drives movements. We propose that this state represents the beginning of the powerstroke on actin and that Pi translocation from the nucleotide pocket triggered by actin binding initiates myosin force generation. This elucidates how actin initiates force generation and movement and may represent a strategy common to many molecular machines.
Structural Motility, Institut Curie, Centre de Recherche, Paris 75248, France; CNRS, UMR144, 26 rue d'Ulm, Cedex 05, Paris 75248, France.
Paola
P
Llinas
Structural Motility, Institut Curie, Centre de Recherche, Paris 75248, France; CNRS, UMR144, 26 rue d'Ulm, Cedex 05, Paris 75248, France.
Tatiana
T
Isabet
Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.
Lin
L
Song
Structural Motility, Institut Curie, Centre de Recherche, Paris 75248, France; CNRS, UMR144, 26 rue d'Ulm, Cedex 05, Paris 75248, France.
Virginie
V
Ropars
Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.
Bin
B
Zong
Structural Motility, Institut Curie, Centre de Recherche, Paris 75248, France; CNRS, UMR144, 26 rue d'Ulm, Cedex 05, Paris 75248, France.
Hannah
H
Benisty
Structural Motility, Institut Curie, Centre de Recherche, Paris 75248, France; CNRS, UMR144, 26 rue d'Ulm, Cedex 05, Paris 75248, France.
Serena
S
Sirigu
Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.
Carl
C
Morris
Structural Motility, Institut Curie, Centre de Recherche, Paris 75248, France; CNRS, UMR144, 26 rue d'Ulm, Cedex 05, Paris 75248, France.
Carlos
C
Kikuti
Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.
Dan
D
Safer
Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA. Electronic address: lsweeney@mail.med.upenn.edu.
H Lee
HL
Sweeney
Structural Motility, Institut Curie, Centre de Recherche, Paris 75248, France; CNRS, UMR144, 26 rue d'Ulm, Cedex 05, Paris 75248, France. Electronic address: anne.houdusse@curie.fr.
Anne
A
Houdusse
D000199:Actins / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002645:Chickens; D018360:Crystallography, X-Ray; D006868:Hydrolysis; D008958:Models, Molecular; D009043:Motor Activity / Q000502:physiology*; D009218:Myosins / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013314:Stress, Mechanical; D013552:Swine
D000199:Actins; D010710:Phosphates; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D009218:Myosins