Complete sequence of human fast‐type and slow‐type muscle myosin‐binding‐protein C (MyBP‐C)

Abstract

Myosin‐binding‐protein C (MyBP‐C) is a myosin‐associated protein of unknown function found in the cross‐bridge‐bearing zone (C region) of A bands in striated muscle. Using a cDNA clone encoding the fast‐type isoform of chicken MyBP‐C, we screened a human fetal muscle cDNA library and isolated clones encoding the full‐length human fast‐type isoform of MyBP‐C. cDNA clones encoding the slow‐type isoform of human MyBP‐C, were also isolated and fully sequenced. Northern‐blot analysis demonstrated skeletal muscle‐specific expression of these gene products. Using human/hamster somatic‐cell hybrids, we were able to map the slow‐type MyBP‐C to human chromosome 12, and the fast‐type MyBP‐C to chromosome 19. The cDNA for human fast‐type MyBP‐C encodes a polypeptide of 1142 amino acids with an expected molecular mass of 128.1 kDa. Comparison of this cDNA with other members of the MyBP family reveals extensive primary‐sequence conservation. Each MyBP‐C contains seven immunoglobulin C2 motifs and three fibronectin type‐III repeats in the arrangement C2‐C2‐C2‐C2‐C2‐III‐III‐C2‐III‐C2. Regions of high identity shared by the chicken and the two human proteins are not restricted to the immunoglobulin and fibronectin motifs. Sequence comparison of all three proteins has allowed us to map a highly conserved region between the first and second C2 motifs, the only large spacer sequence present between motifs in these proteins.

Modulation of myosin filament organization by C-protein family members.

“…However, the changes that are seen in these structures upon the addition of MyBPs are the same as those seen in synthetic thick filaments when MyBPs are added (Huxley, 1963;Koretz, 1979;Yamamoto, 1988). These changes include decreased filament diameter, as well as compaction and disordering of myosin within the filament (Koretz, 1979;Yamamoto, 1988 structures (0.4-0.8 ,um) are still about 50 times wider than synthetic filaments formed in the presence of MyBP (0.013-0.026 ,um) (Koretz, 1979;Yamamoto, 1988 (Einheber and Fischman, 1990;Weber et al, 1993 numerous proteins that are known to bind MyHC including titin, twitchin, skelemin, projectin, M-protein, and myomesin reveals that many of them contain Ig C2 and Fn III repeats (Vaughan et al, 1992), suggesting that sequences within these motifs contain the myosin contact sites. However, because these proteins contain multiple repeats, it is difficult to tell which repeat actually interacts with MyHC.…”

“…Based on their similar amino acid composition and sarcomeric localization, these three proteins have been classified as a family of myosinbinding proteins (MyBP) (Einheber and Fischman, 1990;Vaughan et al, 1993a,b;Weber et al, 1993). Mem-bers of this family contain repeated motifs with homology to the Ig C2 (Ig C2) repeat and the fibronectin type III (Fn III) repeat, as do other MyBPs such as titin, twitchin, and skelemin (Einheber and Fischman, 1990).…”

Tissue-specific Isoforms of Chicken Myomesin Are Generated by Alternative Splicing

“…This value is still significantly higher than the similarities between one of the mentioned M-band-associated proteins and any other muscle protein (5-20% sequence identity) belonging to the immunoglobulin superfamily, like C-protein or titin (Fig. 8, D and E), both of which have a completely different arrangement of class I and II motifs (Fü rst et al, 1992;Labeit et al, 1990;Weber et al, 1993). Therefore, we conclude that myomesin, M-protein, and skelemin are close relatives in the huge immunoglobulin superfamily.…”

Genetic Abnormalities in a Calf with Congenital Increased Muscular Tonus

“…Myosin binding protein C slow type consists of two repetitive domains: 3 fibronectin type‐III repeats and 7 immunoglobulin C2 repeats (Fig 2C), and it is specifically expressed in skeletal muscle 13. It has both structural and regulatory roles in muscle function, providing thick filament stability and modulating contractility through interactions with myosin and actin (OMIM 160794).…”