title: STIL binding to Polo-box 3 of PLK4 regulates centriole duplication.
abstract: Polo-like kinases (PLK) are eukaryotic regulators of cell cycle progression, mitosis and cytokinesis; PLK4 is a master regulator of centriole duplication. Here, we demonstrate that the SCL/TAL1 interrupting locus (STIL) protein interacts via its coiled-coil region (STIL-CC) with PLK4 in vivo. STIL-CC is the first identified interaction partner of Polo-box 3 (PB3) of PLK4 and also uses a secondary interaction site in the PLK4 L1 region. Structure determination of free PLK4-PB3 and its STIL-CC complex via NMR and crystallography reveals a novel mode of Polo-box-peptide interaction mimicking coiled-coil formation. In vivo analysis of structure-guided STIL mutants reveals distinct binding modes to PLK4-PB3 and L1, as well as interplay of STIL oligomerization with PLK4 binding. We suggest that the STIL-CC/PLK4 interaction mediates PLK4 activation as well as stabilization of centriolar PLK4 and plays a key role in centriole duplication.
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Arquint
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Gabryjonczyk
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Imseng
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Raphael
authors.initials: R
authors.lastname: Böhm
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Sauer
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hiller
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Timm
authors.initials: T
authors.lastname: Maier
mesh_terms: D002502:Centrioles / Q000235:genetics* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D050505:Mutant Proteins; C071236:STIL protein, human; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: NMR; X-ray crystallography; biophysics; cell biology; cell cycle; centriole duplication; human; structural biology