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      The cardiomyopathy-associated K15N mutation in tropomyosin alters actin filament pointed end dynamics

      , , , ,
      Archives of Biochemistry and Biophysics
      Elsevier BV

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          Abstract

          <p class="first" id="P1">Correct assembly of thin filaments composed of actin and actin-binding proteins is of crucial importance for properly functioning muscle cells. Tropomyosin (Tpm) mediates the binding of tropomodulin (Tmod) and leiomodin (Lmod) at the slow-growing, or pointed, ends of the thin filaments. Together these proteins regulate thin filament lengths and actin dynamics in cardiac muscle. The K15N mutation in the <i>TPM1</i> gene is associated with familial dilated cardiomyopathy (DCM) but the effect of this mutation on Tpm's function is unknown. In this study, we introduced the K15N mutation in striated muscle α-Tpm (Tpm1.1) and investigated its interaction with actin, Tmod and Lmod. The mutation caused a ∼3-fold decrease in the affinity of Tpm1.1 for actin. The binding of Lmod and Tmod to Tpm1.1-covered actin filaments also decreased in the presence of the K15N mutation. Furthermore, the K15N mutation in Tpm1.1 disrupted the inhibition of actin polymerization and affected the competition between Tmod1 and Lmod2 for binding at the pointed ends. Our data demonstrate that the K15N mutation alters pointed end dynamics by affecting molecular interactions between Tpm1.1, Lmod2 and Tmod1. </p>

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          Author and article information

          Journal
          Archives of Biochemistry and Biophysics
          Archives of Biochemistry and Biophysics
          Elsevier BV
          00039861
          September 2017
          September 2017
          : 630
          : 18-26
          Article
          10.1016/j.abb.2017.07.006
          5568491
          28732641
          f7cf4af7-4dca-4681-a42d-91c9556d7196
          © 2017

          https://www.elsevier.com/tdm/userlicense/1.0/

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