X-ray Diffraction of Muscle labelled with Antibody to C-Protein

Rome, Elizabeth; Offer, Gerald; Pepe, Frank A.

doi:10.1038/newbio244152a0

Cited by 79 publications

(57 citation statements)

References 16 publications

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“…For instance, the doublet at 39.5 and 38.3 nm originates from the actin filament (Huxley and Brown 1967), and has been later attributed to the repeat of troponin along the filament axis (Rome et al 1973b), which gives rise to a reflection sampled by interference effects across the Z line. The doublet at 44.2 and 41.8 nm has been associated with the periodicity of C-protein (Rome 1973a), which lies close to the central region of the thick filament. The split of the reflection is due to interference of the two arrays of Cprotein across the M line.…”

Section: Origin Of the Fine Structurementioning

confidence: 99%

“…Of these, a pair of reflections at 44.2 and 41.8 nm that have been associated to the protein C (Rome et al 1973a), which binds to the myosin filament with a function still to be fully clarified (Moos et al 1975;Moos and Feng 1980;Squire et al 2003). Another pair of reflections at 38.3 and 39.5 nm likely originating from the troponin repeat along the actin filament (Rome et al 1973b).…”

Section: The Muscle At Restmentioning

confidence: 99%

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Recent improvements in small angle x-ray diffraction for the study of muscle physiology

Reconditi¹

2006

Rep. Prog. Phys.

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The molecular mechanism of muscle contraction is one of the most important unresolved problems in Biology and Biophysics. Notwithstanding the great advances of recent years, it is not yet known in detail how the molecular motor in muscle, the class II myosin, converts the free energy of ATP hydrolysis into work by interacting with its track, the actin filament, neither it is understood how the high efficiency in energy conversion depends on the cooperative action of myosin motors working in parallel along the actin filament. Researches in muscle contraction imply the combination of mechanical, biochemical and structural methods in studies that span from tissue to single molecule. Therefore, more than for any other research field, progresses in the comprehension of muscle contraction at molecular level are related to, and in turn contribute to, the advancement of methods in Biophysics.This review will focus on the progresses achieved by time resolved small angle X-ray scattering (SAXS) from muscle, an approach made possible by the highly ordered arrangement of both the contractile proteins myosin and actin in the ca 2 μm long structural unit the sarcomere that repeats along the whole length of the muscle cell. Among the time resolved structural techniques, SAXS has proved to be the most powerful method of investigation, as it allows the molecular motor to be studied in situ, in intact single muscle cells, where it is possible to combine the structural study with fast mechanical methods that synchronize the action of the molecular motors. The latest development of this technique allows Angstrom-scale measurements of the axial movement of the motors that pull the actin filament toward the centre of the sarcomere, by exploiting the X-ray interference between the two arrays of myosin motors in the two halves of the sarcomere.

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Section: Origin Of the Fine Structurementioning

confidence: 99%

Section: The Muscle At Restmentioning

confidence: 99%

Recent improvements in small angle x-ray diffraction for the study of muscle physiology

Reconditi¹

2006

Rep. Prog. Phys.

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“…The first-order myosin meridional reflection, M1, has the contribution of the MyBP-C, which is present in the C zone of the thick filament with an ∼43-nm periodicity (3,23). The second (M2), fourth (M4), and fifth orders (M5) are the so-called forbidden reflections associated with the perturbations of the helical symmetry of the myosin motors in the C-zone of the thick filament (24,25).…”

Section: Sl-tension Relationmentioning

confidence: 99%

Myosin filament activation in the heart is tuned to the mechanical task

Reconditi

Caremani

Pinzauti

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

130

147

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The mammalian heart pumps blood through the vessels, maintaining the dynamic equilibrium in a circulatory system driven by two pumps in series. This vital function is based on the fine-tuning of cardiac performance by the Frank-Starling mechanism that relates the pressure exerted by the contracting ventricle (end systolic pressure) to its volume (end systolic volume). At the level of the sarcomere, the structural unit of the cardiac myocytes, the Frank-Starling mechanism consists of the increase in active force with the increase of sarcomere length (length-dependent activation). We combine sarcomere mechanics and micrometer-nanometer-scale X-ray diffraction from synchrotron light in intact ventricular trabeculae from the rat to measure the axial movement of the myosin motors during the diastole-systole cycle under sarcomere length control. We find that the number of myosin motors leaving the off, ATP hydrolysis-unavailable state characteristic of the diastole is adjusted to the sarcomere length-dependent systolic force. This mechanosensing-based regulation of the thick filament makes the energetic cost of the systole rapidly tuned to the mechanical task, revealing a prime aspect of the Frank-Starling mechanism. The regulation is putatively impaired by cardiomyopathycausing mutations that affect the intramolecular and intermolecular interactions controlling the off state of the motors. myosin filament mechanosensing | heart regulation | small-angle X-ray diffraction | cardiac muscle | Frank-Starling mechanism I n each sarcomere, the structural unit of the skeletal and cardiac muscles, myosin motors arranged in antiparallel arrays in the two halves of the thick myosin-containing filament work cooperatively, generating force and shortening by cyclic ATPdriven interactions with the interdigitating thin actin-containing filaments. The textbook model for the activation of contraction indicates that the binding to actin of myosin motors from the neighboring thick filament is controlled by a calcium-dependent structural change in the thin filament. However, in these muscles at rest, most of the myosin motors are in the off state and packed into helical tracks with 43-nm periodicity on the surface of the thick filaments (1-4), making them unavailable for binding to the thin filament and ATP hydrolysis (5, 6). Recent X-ray diffraction experiments on single fibers from skeletal muscle showed that, in addition to the canonical thin filament activation system, a thick filament mechanosensing mechanism provides a way for selective unlocking of myosin motors during high load contraction (7). This thick filament-based regulation has not yet been shown in cardiac muscle, in which several regulatory systems are significant. In contrast to skeletal muscle, during heart contraction, the internal concentration of Ca 2+ ([Ca 2+ ] i ) may not reach the full activation level, and thus, the mechanical response depends on both [Ca 2+ ] i and the sensitivity of the filaments to Ca 2+ (8, 9). For a given [Ca 2+ ] i , the maximal force i...

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“…Myosin binding protein C (MyBP-C) is a myofilament protein of the intracellular immunoglobulin/ fibronectin superfamily that is located in the "C-zone" of the A-band in seven to nine transverse stripes spaced 43 nm apart (142,661,757). Distinct genes encode for the three isoforms of MyBP-C that are expressed in adult mammalian striated muscle and include fast skeletal, slow skeletal, and cardiac MyBP-C. MYBP3 is the gene that encodes for the cardiac isoform (cMyBP-C) (257), and it is expressed exclusively in cardiac muscle throughout development (256).…”

Section: Thick Filament Accessory Proteins: C-protein (Mybp-c)mentioning

confidence: 99%

Designing Heart Performance by Gene Transfer

Davis¹,

Westfall²,

Townsend³

et al. 2008

Physiological Reviews

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The birth of molecular cardiology can be traced to the development and implementation of high-fidelity genetic approaches for manipulating the heart. Recombinant viral vector-based technology offers a highly effective approach to genetically engineer cardiac muscle in vitro and in vivo. This review highlights discoveries made in cardiac muscle physiology through the use of targeted viral-mediated genetic modification. Here the history of cardiac gene transfer technology and the strengths and limitations of viral and nonviral vectors for gene delivery are reviewed. A comprehensive account is given of the application of gene transfer technology for studying key cardiac muscle targets including Ca2+handling, the sarcomere, the cytoskeleton, and signaling molecules and their posttranslational modifications. The primary objective of this review is to provide a thorough analysis of gene transfer studies for understanding cardiac physiology in health and disease. By comparing results obtained from gene transfer with those obtained from transgenesis and biophysical and biochemical methodologies, this review provides a global view of cardiac structure-function with an eye towards future areas of research. The data presented here serve as a basis for discovery of new therapeutic targets for remediation of acquired and inherited cardiac diseases.

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X-ray Diffraction of Muscle labelled with Antibody to C-Protein

Cited by 79 publications

References 16 publications

Recent improvements in small angle x-ray diffraction for the study of muscle physiology

Recent improvements in small angle x-ray diffraction for the study of muscle physiology

Myosin filament activation in the heart is tuned to the mechanical task

Designing Heart Performance by Gene Transfer

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