Dynamitin mutagenesis reveals protein-protein interactions important for dynactin structure

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Kerstin C MaierTrina A Schroer

Abstract

Dynactin is a highly conserved, multiprotein complex that works in conjunction with microtubule-based motors to power a variety of intracellular motile events. Dynamitin (p50) is a core element of dynactin structure. In the present study, we use targeted mutagenesis to evaluate how dynamitin's different structural domains contribute to its ability to self-associate, interact with dynactin and assemble into a complex with its close binding partner, p24. We show that these interactions involve three distinct structural elements: (i) a previously unidentified dimerization motif in the N-terminal 100 amino acids, (ii) an alpha-helical motif spanning aa 106-162 and (iii) the C-terminal half of the molecule (aa 213-406), which is predicted to fold into an antiparallel alpha-helix bundle. The N-terminal half of dynamitin by itself is sufficient to disrupt dynactin, although very high concentrations are required. The ability of mutations in dynamitin's interaction domains to disrupt dynactin in vitro was found to correlate with their inhibitory effects when expressed in cells. We determined that the dynactin subunit, p24, governs dynamitin oligomerization by binding dynamitin along its length. This suppresses aberrant multimerization a...Continue Reading

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Citations

Jun 26, 2012·BMC Evolutionary Biology·Björn Hammesfahr, Martin Kollmar
May 16, 2014·Molecular Biology of the Cell·Frances Ka Yan CheongTrina A Schroer
Feb 5, 2011·Biochemical and Biophysical Research Communications·Ryo OharaToshihide Yamashita
Aug 5, 2014·The Biochemical Journal·Benoît ChatinFrançoise Le Bouffant
Jul 22, 2014·Journal of Molecular Biology·Hiroshi ImaiTrina A Schroer
Apr 3, 2020·Molecular Biology of the Cell·Kei SaitoYoko Y Toyoshima

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