Tropomodulin Binds Two Tropomyosins: A Novel Model for Actin Filament Capping
Year: 2006
Type: article
Abstract: Tropomodulin, a tropomyosin-binding protein, caps the slow-growing (pointed) end of the actin filament regulating its dynamics. Tropomodulin, therefore, is important for determining cell morphology, cell movement, and muscle contraction. For the first time we show that one tropomodulin molecule simultaneously binds two tropomyosin molecules in a cooperative manner. On the basis of the tropomodulin solution structure and predicted secondary structure, we introduced a series of point mutations in regions important for tropomyosin binding and actin capping. Capping activity of these mutants was assayed by measuring actin polymerization using pyrene fluorescence. Using direct methods (circular dichroism and native gel electrophoresis) for detecting tropomodulin/tropomyosin binding, we localized the second tropomyosin-binding site to residues 109-144. Despite previous reports that the second binding site is for erythrocyte tropomyosin only, we found that both short nonmuscle and long muscle alpha-tropomyosins bind there as well, though with different affinities. We propose a model for actin capping where one tropomodulin molecule can bind to two tropomyosin molecules at the pointed end.
Source: Biochemistry
DOI: 10.1021/bi060899i
Authors: Alla S. Kostyukova, Andy Choy, Brian A. Rapp
Institution: Rutgers, The State University of New Jersey
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Awards: G6707026585, G729906159
OpenAlex ID: W1998806189