2. Academic Validation
  3. An EB1-binding motif acts as a microtubule tip localization signal

An EB1-binding motif acts as a microtubule tip localization signal

  • Cell. 2009 Jul 23;138(2):366-76. doi: 10.1016/j.cell.2009.04.065.
Srinivas Honnappa 1,  Susana Montenegro Gouveia,  Anke Weisbrich,  Fred F Damberger,  Neel S Bhavesh,  Hatim Jawhari,  Ilya Grigoriev,  Frederik J A van Rijssel,  Ruben M Buey,  Aleksandra Lawera,  Ilian Jelesarov,  Fritz K Winkler,  Kurt Wüthrich,  Anna Akhmanova,  Michel O Steinmetz
Affiliations

Affiliation

  • 1 Biomolecular Research, Structural Biology, Paul Scherrer Institut, 5232 Villigen PSI, Switzerland.
PMID: 19632184 DOI: 10.1016/j.cell.2009.04.065
Abstract

Microtubules are filamentous Polymers essential for cell viability. Microtubule plus-end tracking proteins (+TIPs) associate with growing microtubule plus ends and control microtubule dynamics and interactions with different cellular structures during cell division, migration, and morphogenesis. EB1 and its homologs are highly conserved proteins that play an important role in the targeting of +TIPs to microtubule ends, but the underlying molecular mechanism remains elusive. By using live cell experiments and in vitro reconstitution assays, we demonstrate that a short polypeptide motif, Ser-x-Ile-Pro (SxIP), is used by numerous +TIPs, including the tumor suppressor APC, the transmembrane protein STIM1, and the Kinesin MCAK, for localization to microtubule tips in an EB1-dependent manner. Structural and biochemical data reveal the molecular basis of the EB1-SxIP interaction and explain its negative regulation by phosphorylation. Our findings establish a general "microtubule tip localization signal" (MtLS) and delineate a unifying mechanism for this subcellular protein targeting process.

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