title: Structure-function relation of the myosin motor in striated muscle.
abstract: Force and shortening in striated muscle are driven by a structural working stroke in the globular portion of the myosin molecules-the myosin head-that cross-links the myosin-containing filaments and the actin-containing filaments. We use time-resolved X-ray diffraction in single fibers from frog skeletal muscle to link the conformational changes in the myosin head determined at atomic resolution in crystallographic studies with the kinetic and mechanical features of the molecular motor in the preserved sarcomeric structure. Our approach exploits the improved brightness and collimation of the X-ray beams of the third generation synchrotrons by using X-ray interference between the two arrays of myosin heads in each bipolar myosin filament to measure with A sensitivity the axial motions of myosin heads in situ during the synchronous execution of the working stroke elicited by rapid decreases in length or load imposed during an active isometric contraction. Changes in the intensity and interference-fine structure of the axial X-ray reflections following the mechanical perturbation allowed to establish the average conformation of the myosin heads during the active isometric contraction and the extent of tilt during the elastic response and during the subsequent working stroke. The myosin working stroke is 12 nm at low loads, which is consistent with crystallographic studies, while it is smaller and slower at higher loads. The load dependence of the size and speed of the myosin working stroke is the molecular determinant of the macroscopic performance and efficiency of muscle.
authors.affiliation: Laboratorio di Fisiologia, DBAG, Università di Firenze, 50019 Sesto Fiorentino, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Reconditi
authors.forename: Marco
authors.initials: M
authors.lastname: Linari
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lucii
authors.forename: Alex
authors.initials: A
authors.lastname: Stewart
authors.forename: Yin-Biao
authors.initials: YB
authors.lastname: Sun
authors.forename: Theyencheri
authors.initials: T
authors.lastname: Narayanan
authors.forename: Tom
authors.initials: T
authors.lastname: Irving
authors.forename: Gabriella
authors.initials: G
authors.lastname: Piazzesi
authors.forename: Malcolm
authors.initials: M
authors.lastname: Irving
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lombardi
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D007537:Isometric Contraction / Q000502:physiology; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry*; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000648:ultrastructure; D011898:Ranidae; D024744:Skeletal Muscle Myosins / Q000737:chemistry* / Q000502:physiology*; D013329:Structure-Activity Relationship; D017356:Synchrotrons
chemical_list: D020409:Molecular Motor Proteins; D024744:Skeletal Muscle Myosins