Nadezhdina Elena S.

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Nadezhdina
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Elena S.
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  • Article
    Phosphorylation controls autoinhibition of cytoplasmic linker protein-170
    (American Society for Cell Biology, 2010-06-02) Lee, Ho-Sup ; Komarova, Yulia A. ; Nadezhdina, Elena S. ; Anjum, Rana ; Peloquin, John G. ; Schober, Joseph M. ; Danciu, Oana ; van Haren, Jeffrey ; Galjart, Niels ; Gygi, Steven P. ; Akhmanova, Anna ; Borisy, Gary G.
    Cytoplasmic linker protein (CLIP)-170 is a microtubule (MT) plus-end-tracking protein that regulates MT dynamics and links MT plus ends to different intracellular structures. We have shown previously that intramolecular association between the N and C termini results in autoinhibition of CLIP-170, thus altering its binding to MTs and the dynactin subunit p150Glued (J. Cell Biol. 2004: 166, 1003–1014). In this study, we demonstrate that conformational changes in CLIP-170 are regulated by phosphorylation that enhances the affinity between the N- and C-terminal domains. By using site-directed mutagenesis and phosphoproteomic analysis, we mapped the phosphorylation sites in the third serine-rich region of CLIP-170. A phosphorylation-deficient mutant of CLIP-170 displays an "open" conformation and a higher binding affinity for growing MT ends and p150Glued as compared with nonmutated protein, whereas a phosphomimetic mutant confined to the "folded back" conformation shows decreased MT association and does not interact with p150Glued. We conclude that phosphorylation regulates CLIP-170 conformational changes resulting in its autoinhibition.