Alteration of myosin cross bridges by phosphorylation of myosin-binding protein C in cardiac muscle
Alteration of myosin cross bridges by phosphorylation of myosin-binding protein C in cardiac muscle
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DOI：
10.1073/pnas.93.17.8999
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发表时间：
1996-08-20
影响因子：
11.1
通讯作者：
Winegrad, S
中科院分区：
文献类型：
--
作者：
Weisberg, A;Winegrad, S
In addition to the contractile proteins actin and myosin, contractile filaments of striated muscle contain other proteins that are important for regulating the structure and the interaction of the two force-generating proteins, In the thin filaments, troponin and tropomyosin form a Ca-sensitive trigger that activates normal contraction when intracellular Ca is elevated. In the thick filament, there are several myosin-binding proteins whose functions are unclear. Among these is the myosin-binding protein C (MBP-C), The cardiac isoform contains four phosphorylation sites under the control of cAMP and calmodulin-regulated kinases, whereas the skeletal isoform contains only one such site, suggesting that phosphorylation in cardiac muscle has a specific regulatory function, We isolated natural thick filaments from cardiac muscle and, using electron microscopy and optical diffraction, determined the effect of phosphorylation of MBP-C on cross bridges. The thickness of the filaments that had been treated with protein kinase A was increased where cross bridges were present, No change occurred in the central bare zone that is devoid of cross bridges, The intensity of the reflections along the 43-nm layer line, which is primarily due to the helical array of cross bridges, was increased, and the distance of the first peak reflection from the meridian along the 43-nm layer line was decreased, The results indicate that phosphorylation of MBP-C (i) extends the cross bridges from the backbone of the filament and (ii) increases their degree of order and/or alters their orientation, These changes could alter rate constants for attachment to and detachment from the thin filament and thereby modify force production in activated cardiac muscle.
