Tropomodulins and tropomodulin/tropomyosin interactions

The tropomodulins are a family of proteins that cap the slow-growing (pointed) end of actin filaments and require tropomyosin for optimal function. Tropomodulin is an elongated molecule with a molecular mass of about 40 kDa. The C-terminal half of tropomodulin contains one compact cooperatively melting domain, whereas the N-terminal half has no cooperatively melting structure. The N-terminal half of tropomodulin contains two tropomysin-binding sites and a tropomyosin-dependent actin-binding site, the tropomyosin-independent actin-binding site being located at the C terminus. One tropomodulin molecule binds two tropomyosin molecules, and thus one molecule of tropomodulin is necessary and sufficient for capping at the pointed end. Tropomyosin/tropomodulin interactions are isoform specific. Differences in tropomyosin affinity for the two binding sites in tropomodulin may regulate its correct positioning at the pointed end as well as effectiveness of capping the actin filament.