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Molecular basis of tropomyosin binding to tropomodulin, an actin-capping protein.

Molecular basis of tropomyosin binding to tropomodulin, an actin-capping protein. Research Abstract Details 

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  • Molecular basis of tropomyosin binding to tropomodulin, an actin-capping protein. Abstract Text:

    alla s kostyukovaAlla S Kostyukova,sarah e hitchcock-degregoriSarah E Hitchcock-Degregori,norma j greenfieldNorma J Greenfield,alla s kostyukovaAlla S Kostyukova,sarah e hitchcock-degregoriSarah E Hitchcock-Degregori,norma j greenfieldNorma J Greenfield,

    The tropomodulin (Tmod) family of proteins that cap the pointed, slow-growing end of actin filaments require tropomyosin (TM) for optimal function. Earlier studies identified two regions in Tmod1 that bind the N terminus of TM, though the ability of different isoforms to bind the two sites is controversial. We used model peptides to determine the affinity and define the specificity of the highly conserved N termini of three short, non-muscle TMs (alpha, gamma, delta-TM) for the two Tmod1 binding sites using circular dichroism spectroscopy, native gel electrophoresis, and chemical crosslinking. All TM peptides have high affinity for the second Tmod1 binding site (within residues 109-144; alpha-TM, 2.5 nM; gamma-TM, delta-TM, 40-90 nM), but differ >100-fold for the first site (residues 1-38; alpha-TM, 90 nM; undetectable at 10 microM, gamma-TM, delta-TM). Residue 14 (R in alpha; Q in gamma and delta) and, to a lesser extent, residue 4 (S in alpha; T in gamma and delta) are primarily responsible for the differences. The functional consequence of the sequence differences is reflected in more effective inhibition of actin filament elongation by full-length alpha-TMs than gamma-TM in the presence of Tmod1. The binding sites of the two Tmod1 peptides on a model TM peptide differ, as defined by comparing (15)N,(1)H HSQC spectra of a (15)N-labeled model TM peptide in both the absence and presence of Tmod1 peptide. The NMR and CD studies show that there is an increase in alpha-helix upon Tmod1-TM complex formation, indicating that intrinsically disordered regions of the two proteins become ordered upon binding. A model proposed for the binding of Tmod to actin and TM at the pointed end of the filament shows how the Tmod-TM accentuates the asymmetry of the pointed end and suggests how subtle differences among TM isoforms may modulate actin filament dynamics.

    Molecular basis of tropomyosin binding to tropomodulin, an actin-capping protein. Publishing Authors By Initials

    as kostyukovaAS Kostyukova,se hitchcock-degregoriSE Hitchcock-Degregori,nj greenfieldNJ Greenfield,as kostyukovaAS Kostyukova,se hitchcock-degregoriSE Hitchcock-Degregori,nj greenfieldNJ Greenfield,

    For similar macromolecular substances: polymers: biopolymers: microfilament proteins: tropomyosin research abstracts see: macromolecular substances: polymers: biopolymers: microfilament proteins: tropomyosin research

    PUBMED ID PMID:

    MEDLINE DATE:

    Molecular basis of tropomyosin binding to tropomodulin, an actin-capping protein. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Journal of molecular biology

    VOLUME: 372

    Page Numbers: 608-18

    Journal Abbreviation: J. Mol. Biol.

    ISSN: 0022-2836

    DAY: 2

    MONTH: 06

    YEAR: 2007

    Molecular basis of tropomyosin binding to tropomodulin, an actin-capping protein. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 2985088

    Molecular basis of tropomyosin binding to tropomodulin, an actin-capping protein. Keywords Mesh Terms:

    KEYWORDS: Tropomyosin

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Molecular basis of tropomyosin binding to tropomodulin, an actin-capping protein. Information

    Substance Name: Tropomyosin

    Registry Number: 0

    Grant and Affiliation Information for Molecular basis of tropomyosin binding to tropomodulin, an actin-capping protein.

    AFFILIATION: Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.

    Country: England

    England Research PublicationEngland Research Publication

    AGENCY: United States NIGMS

    GRANT: GM63257

    ACRONYM: GM

    MEDLINETA: J Mol Biol

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    Number Hits: 0

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