CA2-CALMODULIN BINDING TO MOUSE ALPHA-1 SYNTROPHIN - SYNTROPHIN IS ALSO A CA2+-BINDING PROTEIN()

Syntrophins are peripheral membrane proteins which have been found ass ociated with dystrophin, the protein product of the Duchenne muscular dystrophy gene locus. Mouse alpha 1 syntrophin binds the COOH-terminal domain of dystrophin, and calmodulin inhibits this interaction in a C a2+-dependent fashion. Where calmodulin binds to syntrophin was invest igated by constructing fusion proteins containing different regions of syntrophin's sequence. Syntrophin contains at least two regions which bind calmodulin in different ways. The COOH-terminal 24 residues cont ain a Ca2+-calmodulin binding site, named CBSC, which binds calmodulin with an apparent affinity of 18 nM and which is highly conserved in a ll syntrophins. The amino-terminal 174 residue section of syntrophin c ontains other calmodulin binding, and binding occurs in either the pre sence or absence of Ca2+ with an apparent affinity of 100 nM. Syntroph in was shown to bind Ca2+ at two or more sites residing in the amino-t erminal 274 residues, and Ca2+ binding to syntrophin affects calmoduli n binding at high concentrations of syntrophin. Syntrophin A (residues 4-274) is predominantly a dimer in EGTA. A model of syntrophin's comp lex interactions with itself (i.e., oligomerization), calmodulin, and Ca2+ is presented.