title: An EB1-binding motif acts as a microtubule tip localization signal.
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.
authors.affiliation: Biomolecular Research, Structural Biology, Paul Scherrer Institut, 5232 Villigen PSI, Switzerland.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Honnappa
authors.forename: Susana Montenegro
authors.initials: SM
authors.lastname: Gouveia
authors.forename: Anke
authors.initials: A
authors.lastname: Weisbrich
authors.forename: Fred F
authors.initials: FF
authors.lastname: Damberger
authors.forename: Neel S
authors.initials: NS
authors.lastname: Bhavesh
authors.forename: Hatim
authors.initials: H
authors.lastname: Jawhari
authors.forename: Ilya
authors.initials: I
authors.lastname: Grigoriev
authors.forename: Frederik J A
authors.initials: FJ
authors.lastname: van Rijssel
authors.forename: Ruben M
authors.initials: RM
authors.lastname: Buey
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Lawera
authors.forename: Ilian
authors.initials: I
authors.lastname: Jelesarov
authors.forename: Fritz K
authors.initials: FK
authors.lastname: Winkler
authors.forename: Kurt
authors.initials: K
authors.lastname: Wüthrich
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
authors.forename: Michel O
authors.initials: MO
authors.lastname: Steinmetz
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000378:metabolism; D008870:Microtubules / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D021382:Protein Sorting Signals; D016415:Sequence Alignment
chemical_list: C405804:EB1 microtubule binding proteins; D008869:Microtubule-Associated Proteins; D021382:Protein Sorting Signals