Tropomodulin

Tropomodulin (TMOD) is a protein which binds and caps the minus end of actin (the "pointed" end), regulating the length of actin filaments in muscle and non-muscle cells.

The protein functions by physically blocking the spontaneous dissociation of ADP-bound actin monomers from the minus end of the actin fibre. This, along with plus end capping proteins, such as capZ stabilise the structure of the actin filament. End capping is particularly important when long-lived actin filaments are necessary, for example: in myofibrils. Inhibition of tropomodulin capping activity leads to dramatic increase in thin filament length from its pointed end.

Actin filaments have two differing ends where one is the fast-acting barbed end and the other is the slow growing pointed end. Since TMOD binds to the pointed end of actin it is essential in cell morphology, cell movement, and muscle contraction. TMOD has been identified as an erythrocyte with 359 amino acids and it is a globular protein. When tropomyosin is not present Tropomodulin also assists in partially inhibiting elongation and depolymerization at the pointed filament ends. The N-terminal of Tropomodulin is rod shaped. This portion then binds to the N-terminal part of the two tropomyosin that are on the opposite part of the actin filaments in the muscle and nonmuscle cells. TMOD is able to have high-affinity binding through low-affinity interactions because of its ability to control subunit exchange of the pointed end of the actin filaments. When looking at epithelial cells Tropomodulin sustains F-actin in the lateral cell membranes and the adherens junction. Tropomodulin binds exclusively to the pointed filament ends and not to actin monomers or alongside actin filaments. Tropomodulin is a 40-kD tropomyosin-binding protein that was originally isolated from the red blood cell membrane skeleton. Tropomodulin is associated with Leiomodin as homologous proteins because both proteins play a role in muscle sarcomere thin filament formation and maintenance. An ortholog that is identified with TMOD and structurally similar  is UNC-94. Where the UNC-94 protein is capping on the minus end of the actin filament. This protein like TMOD depends on the presence of tropomyosin in order to function properly.