Smooth muscle caldesmon is an extended flexible monomeric protein in solution that can readily undergo reversible intra- and intermolecular sulfhydryl cross-linking. A mechanism for caldesmon's F-actin bundling activity.
Caldesmon is a major F-actin binding protein of smooth muscle that has been implicated as a component of a thin filament regulatory system. Chicken gizzard caldesmon consists of polypeptides of Mr-135,000 and 140,000 which are closely related as determined by analysis of cyanogen bromide cleavage fragments. It is a highly extended flexible protein having a contour length of about 146 nm and a secondary structure composed primarily of random coil. Physical and chemical cross-linking data suggest that caldesmon exists as a monomer in solution. The cysteine content of caldesmon was determined to be 2 residues/polypeptide. Remarkably, in solution it readily undergoes sulfhydryl oxidation to form either an internal disulfide bridge in the protein or cross-links between individual polypeptides to form dimers, trimers, tetramers, etc. The internally cross-linked species have a smaller Stokes radius than the reduced molecules, indicating that the cross-link "trapped" the molecule in a compact conformation. Oxidized protein containing caldesmon oligomers is a potent F-actin bundling protein. Complete reduction of caldesmon abolishes the F-actin bundling activity. Since a vast excess of reducing agent is required to convert caldesmon from an oxidized to reduced state, it may exist in either state in vivo. Thus, the ability of caldesmon to undergo reversible sulfhydryl cross-linking, and thereby reversible F-actin cross-linking, may be of physiological significance.
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D002645:Chickens; D003432:Cross-Linking Reagents; D003488:Cyanogen Bromide; D003545:Cysteine / Q000032:analysis; D004220:Disulfides / Q000378:metabolism; D005895:Gizzard, Avian / Q000032:analysis; D008970:Molecular Weight; D009130:Muscle, Smooth / Q000032:analysis*; D010084:Oxidation-Reduction; D010446:Peptide Fragments; D011487:Protein Conformation; D011817:Rabbits; D012996:Solutions; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D000199:Actins; D002148:Calmodulin-Binding Proteins; D003432:Cross-Linking Reagents; D004220:Disulfides; D010446:Peptide Fragments; D012996:Solutions; D013438:Sulfhydryl Compounds; D003545:Cysteine; D003488:Cyanogen Bromide