Journal article
Effect of the Structure of the N Terminus of Tropomyosin on Tropomodulin Function
The Journal of biological chemistry, Vol.279(7), pp.5066-5071
02/13/2004
Handle:
https://hdl.handle.net/2376/109486
PMID: 14660556
Abstract
Tropomodulins (Tmod) bind to the N terminus of tropomyosin and cap the pointed end of actin filaments. Tropomyosin alone also inhibits the rate of actin depolymerization at the pointed end of filaments. Here we have defined 1) the structural requirements of the N terminus of tropomyosin important for regulating the pointed end alone and with erythrocyte Tmod (Tmod1), and 2) the Tmod1 subdomains required for binding to tropomyosin and for regulating the pointed end. Changes in pyrene-actin fluorescence during polymerization and depolymerization were measured with actin filaments blocked at the barbed end with gelsolin. Three tropomyosin isoforms differently influence pointed end dynamics. Recombinant TM5a, a short non-muscle α-tropomyosin, inhibited depolymerization. Recombinant (unacetylated) TM2 and N-acetylated striated muscle TM (stTM), long α-tropomyosin isoforms with the same N-terminal sequence, different from TM5a, also inhibited depolymerization but were less effective than TM5a. All blocked the pointed end with Tmod1 in the order of effectiveness TM5a >stTM >TM2, showing the importance of the N-terminal sequence and modification. Tmod1-(1–344), lacking the C-terminal 15 residues, did not nucleate polymerization but blocked the pointed end with all three tropomyosin isoforms as does a shorter fragment, Tmod1-(1–92), lacking the C-terminal “capping” domain though higher concentrations were required. An even shorter fragment, Tmod1-(1–48), bound tropomyosin but did not influence actin filament elongation. Tropomyosin-Tmod may function to locally regulate cytoskeletal dynamics in cells by stabilizing actin filaments.
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Details
- Title
- Effect of the Structure of the N Terminus of Tropomyosin on Tropomodulin Function
- Creators
- Alla S Kostyukova - Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854Sarah E Hitchcock-DeGregori - Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854
- Publication Details
- The Journal of biological chemistry, Vol.279(7), pp.5066-5071
- Academic Unit
- Chemical Engineering and Bioengineering, School of
- Publisher
- Elsevier Inc
- Identifiers
- 99900547625801842
- Language
- English
- Resource Type
- Journal article