Practice question

Pointed end regulation ensures uniform thin filament length in sarcomeres and stability of short filaments in erythrocyte cytoskeleton. Tropomodulin Tmod family capping proteins bind with nanomolar affinity to pointed minus end, preventing subunit addition and dissociation. Domain structure includes two tropomyosin binding amphipathic helices at N terminus residues 1 to 135 that interact with N terminus of tropomyosin coating filament, and C terminal leucine rich repeat domain residues 160 to 359 forming horseshoe that caps terminal actin subunits contacting subdomain 1 and 3 interface. By clamping pointed end and anchoring tropomyosin, tropomodulin locks filament length after elongation by leiomodin during development, which acts as nucleator competing at same site. Knockout in cardiomyocytes results in elongated thin filaments and dilated cardiomyopathy. Protein does not sequester G actin like thymosin, does not accelerate barbed end depolymerization which is cofilin gelsolin action, and does not bundle filaments like fascin, its specific activity capping minus end and stabilizing length.