Abstract
Small angle X-ray fiber diffraction is the method of choice for obtaining molecular level structural information from striated muscle fibers under hydrated physiological conditions. For many decades this technique had been used primarily for investigating basic biophysical questions regarding muscle contraction and regulation and its use confined to a relatively small group of expert practitioners. Over the last 20 years, however, X-ray diffraction has emerged as an important tool for investigating the structural consequences of cardiac and skeletal myopathies. In this review we show how simple and straightforward measurements, accessible to non-experts, can be used to extract biophysical parameters that can help explain and characterize the physiology and pathology of a given experimental system. We provide a comprehensive guide to the range of the kinds of measurements that can be made and illustrate how they have been used to provide insights into the structural basis of pathology in a comprehensive review of the literature. We also show how these kinds of measurements can inform current controversies and indicate some future directions.
Highlights
X-ray diffraction is the only technique that can provide global molecular-level structural information from striated muscle under hydrated, physiological conditions on the physiologically relevant milli-second time scale
At full thick-thin filament overlap, intensification of ALL6, ALL7, the tropomyosin reflection and the M3 meridional reflection were blunted in the mutant myocardium as compared to controls but were indistinguishable in overstretched muscle indicating that the replacement of just one amino acid in the skeletal muscle α-actin protein was sufficient to impair actin conformational changes and tropomyosin movement during activation that would allow strong binding of myosin molecules leading to impaired contractility
One must keep in mind that it is a lowresolution technique compared to other structural techniques such as X-ray crystallography, NMR, and Cryo-EM
Summary
X-ray diffraction is the only technique that can provide global molecular-level structural information from striated muscle under hydrated, physiological conditions on the physiologically relevant milli-second time scale. Some of the best evidence for the steric blocking mechanism of thin filament regulation [9–11] came from X-ray diffraction studies [12–17]. These studies all indicated azimuthal movement of tropomyosin on the thin filament upon binding of calcium to troponin to unblock myosin binding sites on actin. The widespread availability of mouse models for many skeletal muscle diseases has motivated recent X-ray diffraction studies of mouse leg muscles to study the structural mechanisms of contraction and relaxation in healthy muscle [24–28] and to investigate the pathological basis of skeletal myopathies using transgenic mouse models [29–34]. We show how these measurements can inform current controversies and indicate some future directions
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