MUSCLE-SPECIFIC CALPAIN, P94, INTERACTS WITH THE EXTREME C-TERMINAL REGION OF CONNECTIN, A UNIQUE REGION FLANKED BY 2 IMMUNOGLOBULIN-C2 MOTIFS

Using the yeast two-hybrid system, we have recently reported that skel etal muscle-specific calpain, p94, binds specifically to connectin (or titin), a gigantic muscle elastic protein. Connectin has at least two binding sites for p94; one is at the N-2-line region and the other is at the extreme C-terminus. In order to analyze the interaction betwee n p94 and the C-terminus of connectin, we examined the C-terminal sequ ence of human skeletal muscle connectin. The sequence was essentially identical to that of heart muscle reported by Labeit and Kolmerer (199 5, Science 270, 293-296), and the minimal binding site for p94 contain ed two IgC2 motifs and the intervening sequence called ''M-is7''. The exon encoding M-is7 is reported to be alternatively spliced depending on muscle tissues, resulting in the existence of both types of connect in with and without M-is7. However, the C-terminal region of connectin bound to p94 through M-is7. Our results suggest that the interaction between p94 and the C-terminus of skeletal muscle-type connectin is in volved in tissue-specific myofibriogenesis. (C) 1997 Academic Press.