X-RAY INTERFERENCE STUDIES OF TROPONIN MOVEMENTS DURING MUSCLE ACTIVATION

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Vertebrate skeletal muscle is switched on by the action of calcium ions binding to the regulatory protein troponin, part of a complex in the actin-containing filaments that actively slide past the myosin filaments during contraction. This binding alters the position of the second regulatory protein tropomyosin, which controls access of the myosin crossbridges to the underlying actin filaments, allowing tension development. It is well-established that tropomyosin changes its azimuthal position on actin during activation, but how this is brought about is at present unknown. The high-resolution crystallographic structure of troponin has been solved recently, suggesting that part of that structure could undergo a tilting movement to move tropomyosin. This might show up as small changes in the axial position of the center of mass of troponin that could be measured by studying the interference fine structure of the 385A meridional reflections from the axial repeat of troponin along actin filaments. This fine structure is generated by symmetrical positioning of actin filaments on either side of the Z-lines, and changes in such fine structure enable one to measure changes in axial position with sub-nanometer accuracy. We have already had considerable successful experience in applying this technique to measurements of the detailed behavior of myosin crossbridges during muscle contraction (see attached publications). We now need considerably more data, to obtain a convincing picture of the phenomenon and to study it in a time-resolved manner, so as to correlate the changes