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STIL binding to Polo-box 3 of PLK4 regulates centriole duplication.

Arquint C, Gabryjonczyk AM, Imseng S, Böhm R, Sauer E, Hiller S, Nigg EA, Maier T - Elife (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Biozentrum, University of Basel, Basel, Switzerland.

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.

No MeSH data available.


Related in: MedlinePlus

PB3 adopts a canonical Polo-box fold.(A) Comparison of the fold of PLK4-PB3 (lightblue) to the folds of PB1 (1.7 Å rmsd, 72 Cα) and PB2 (1.3 Å rmsd, 79 Cα) of PLK1 (PDB accession code: 1Q4O, left) (Cheng et al., 2003) and of PB1 (2.5 Å rmsd, 66 Cα) and PB2 (1.4 Å rmsd, 68 Cα) of PLK4 (PDB accession code: 4N9J, right)(Park et al., 2014) by structural superposition (Krissinel and Henrick, 2004). For the alignments the crystal structure of PLK4-PB3 was used. (B) Crystal structure of the domain-swapped dimer of the PLK4-PB3 murine ortholog SAK in cartoon representation (Leung et al., 2002).DOI:http://dx.doi.org/10.7554/eLife.07888.014
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fig5s4: PB3 adopts a canonical Polo-box fold.(A) Comparison of the fold of PLK4-PB3 (lightblue) to the folds of PB1 (1.7 Å rmsd, 72 Cα) and PB2 (1.3 Å rmsd, 79 Cα) of PLK1 (PDB accession code: 1Q4O, left) (Cheng et al., 2003) and of PB1 (2.5 Å rmsd, 66 Cα) and PB2 (1.4 Å rmsd, 68 Cα) of PLK4 (PDB accession code: 4N9J, right)(Park et al., 2014) by structural superposition (Krissinel and Henrick, 2004). For the alignments the crystal structure of PLK4-PB3 was used. (B) Crystal structure of the domain-swapped dimer of the PLK4-PB3 murine ortholog SAK in cartoon representation (Leung et al., 2002).DOI:http://dx.doi.org/10.7554/eLife.07888.014

Mentions: The structure of the human PLK4-PB3 resembles the canonical structures of related Polo-boxes (Figure 5—figure supplement 4A). It aligns structurally well with both Polo-boxes of the PLK1-PBD (Cheng et al., 2003; Elia et al., 2003b). PLK1-PB2 is a close structural homologue (1.3 Å rmsd, 79 Cα), with minor differences only in the linker to the α-helix. PLK1-PB1 is slightly more divergent, in that the C-terminal end of the α1-helix is bent towards the region, where STIL-CC is bound in PLK4-PB3. PLK4-PB3 also aligns with its two companion Polo-boxes of the PLK4-PB1/PB2 domain (Slevin et al., 2012; Park et al., 2014). Structural divergence to PLK4-PB1 occurs in the β-hairpin region between β3-β4, which gives PLK4-PB1 its unique winged structure, as well as in the linker between β5-β6. A major distinction between PLK4-PB3 and PLK4-PB2 is the length of helix α1, which extends beyond the β-sheet in PLK4-PB2.


STIL binding to Polo-box 3 of PLK4 regulates centriole duplication.

Arquint C, Gabryjonczyk AM, Imseng S, Böhm R, Sauer E, Hiller S, Nigg EA, Maier T - Elife (2015)

PB3 adopts a canonical Polo-box fold.(A) Comparison of the fold of PLK4-PB3 (lightblue) to the folds of PB1 (1.7 Å rmsd, 72 Cα) and PB2 (1.3 Å rmsd, 79 Cα) of PLK1 (PDB accession code: 1Q4O, left) (Cheng et al., 2003) and of PB1 (2.5 Å rmsd, 66 Cα) and PB2 (1.4 Å rmsd, 68 Cα) of PLK4 (PDB accession code: 4N9J, right)(Park et al., 2014) by structural superposition (Krissinel and Henrick, 2004). For the alignments the crystal structure of PLK4-PB3 was used. (B) Crystal structure of the domain-swapped dimer of the PLK4-PB3 murine ortholog SAK in cartoon representation (Leung et al., 2002).DOI:http://dx.doi.org/10.7554/eLife.07888.014
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530586&req=5

fig5s4: PB3 adopts a canonical Polo-box fold.(A) Comparison of the fold of PLK4-PB3 (lightblue) to the folds of PB1 (1.7 Å rmsd, 72 Cα) and PB2 (1.3 Å rmsd, 79 Cα) of PLK1 (PDB accession code: 1Q4O, left) (Cheng et al., 2003) and of PB1 (2.5 Å rmsd, 66 Cα) and PB2 (1.4 Å rmsd, 68 Cα) of PLK4 (PDB accession code: 4N9J, right)(Park et al., 2014) by structural superposition (Krissinel and Henrick, 2004). For the alignments the crystal structure of PLK4-PB3 was used. (B) Crystal structure of the domain-swapped dimer of the PLK4-PB3 murine ortholog SAK in cartoon representation (Leung et al., 2002).DOI:http://dx.doi.org/10.7554/eLife.07888.014
Mentions: The structure of the human PLK4-PB3 resembles the canonical structures of related Polo-boxes (Figure 5—figure supplement 4A). It aligns structurally well with both Polo-boxes of the PLK1-PBD (Cheng et al., 2003; Elia et al., 2003b). PLK1-PB2 is a close structural homologue (1.3 Å rmsd, 79 Cα), with minor differences only in the linker to the α-helix. PLK1-PB1 is slightly more divergent, in that the C-terminal end of the α1-helix is bent towards the region, where STIL-CC is bound in PLK4-PB3. PLK4-PB3 also aligns with its two companion Polo-boxes of the PLK4-PB1/PB2 domain (Slevin et al., 2012; Park et al., 2014). Structural divergence to PLK4-PB1 occurs in the β-hairpin region between β3-β4, which gives PLK4-PB1 its unique winged structure, as well as in the linker between β5-β6. A major distinction between PLK4-PB3 and PLK4-PB2 is the length of helix α1, which extends beyond the β-sheet in PLK4-PB2.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Biozentrum, University of Basel, Basel, Switzerland.

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.

No MeSH data available.


Related in: MedlinePlus