Earning stripes: myosin binding protein-C interactions with actin.
Myosin binding protein-C (MyBP-C) was first discovered as an impurity during the purification of myosin from skeletal muscle. However, soon after its discovery, MyBP-C was also shown to bind actin. While the unique functional implications for a protein that could cross-link thick and thin filaments together were immediately recognized, most early research nonetheless focused on interactions of MyBP-C with the thick filament. This was in part because interactions of MyBP-C with the thick filament could adequately explain most (but not all) effects of MyBP-C on actomyosin interactions and in part because the specificity of actin binding was uncertain. However, numerous recent studies have now established that MyBP-C can indeed bind to actin through multiple binding sites, some of which are highly specific. Many of these interactions involve critical regulatory domains of MyBP-C that are also reported to interact with myosin. Here we review current evidence supporting MyBP-C interactions with actin and discuss these findings in terms of their ability to account for the functional effects of MyBP-C. We conclude that the influence of MyBP-C on muscle contraction can be explained equally well by interactions with actin as by interactions with myosin. However, because data showing that MyBP-C binds to either myosin or actin has come almost exclusively from in vitro biochemical studies, the challenge for future studies is to define which binding partner(s) MyBP-C interacts with in vivo.
Department of Cellular and Molecular Medicine, University of Arizona, Medical Research Building, 1656 East Mabel Street, Tucson, AZ, 85724-5217, USA.
Sabine J
SJ
van Dijk
Kristina L
KL
Bezold
Samantha P
SP
Harris
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D012518:Sarcomeres / Q000378:metabolism* / Q000648:ultrastructure; D000099163:Myosin Binding Protein C
D000199:Actins; D002352:Carrier Proteins; D000099163:Myosin Binding Protein C