Polo-like kinases (Plks) belong to the serine/threonine kinase subfamily, and are characterized by the presence of the signature motif called Polo-box domain. Plks are key regulators of cell cycle and cell division in eukaryotes [, ]. Unicellular organisms contain one Plk whereas higher eukaryotes have as many as four Plks: Plk1, Plk2, Plk3 andPlk4.Plk4 (also called Sak) is the most structurally divergent member of the Plks. It plays a pivotal role in centriole duplication [, , , , ]and is required for centriolar satellite function and ciliogenesis []. Substrates identified for Plk4 include Cdc25C and Chk2 [, ].
Cep85 is a centrosomal protein of 85kDa []. It is a centriole duplication factor that directly interacts with STIL. It is essential for efficient centriolar targeting of STIL, PLK4 activation and faithful daughter centriole assembly [].
In metazoans, Plk4 kinases control daughter centriole assembly. Plk4 homologues have an N-terminal kinase domain, a C-terminal polo box, and a central domain termed the 'cryptic polo box' (CPB) that has been shown to dimerize, to be sufficient for centriole localization and to be required for Plk4 to promote centriole assembly. Probable serine/threonine-protein kinase zyg-1 () (ZYG-1) is a Plk4 homlogue found in C. elegans. Crystal structure for the CPB of C. elegans ZYG-1, reveals that it forms a Z-shaped dimer containing an intermolecular β-sheet with an extended basic surface patch. Electrostatic interactions between the basic patch on the ZYG-1 CPB dimer and the SPD-2 acidic region dock ZYG-1 onto centrioles to promote new centriole assembly. ZYG-1 CPB contains two tandem polo boxes (PB1 and PB2), each containing a six-stranded β-sheet with an α-helix packed against one side []. This entry represents PB1.
In metazoans, Plk4 kinases control daughter centriole assembly. Plk4 homologs have an N-terminal kinase domain, a C-terminal polo box, and a central domain termed the 'cryptic polo box' (CPB) that has been shown to dimerize, to be sufficient for centriole localization and to be required for Plk4 to promote centriole assembly. Probable serine/threonine-protein kinase zyg-1 () (ZYG-1) is a Plk4 homlog found in C. elegans. Crystal structure for the CPB of C. elegans ZYG-1, reveals that it forms a Z-shaped dimer containing an intermolecular β-sheet with an extended basic surface patch. Electrostatic interactions between the basic patch on the ZYG-1 CPB dimer and the SPD-2 acidic region dock ZYG-1 onto centrioles to promote new centriole assembly. ZYG-1 CPB contains two tandem polo boxes (PB1 and PB2), each containing a six-stranded β-sheet with an α-helix packed against one side []. This entry represents PB2.
Centrosomal protein of 152kDa (Cep152) acts as a scaffold for recruitment of centriole regulators, Plk4 and CPAP, to the centrosome [, ]. In multiciliated cell (MCCs), the basal bodies of the motile cilia are derived from centroles, which are amplified in a structure known as the deuterostome. Cep152 is required for the centriole biogenesis in deuterostome [].
The polo-like Ser/Thr kinases (Plk1, Plk2/Snk, Plk3/Prk/Fnk, Plk4/Sak, and the inactive kinase Plk5) play various roles in cytokinesis and mitosis. At their C terminus, they contain a tandemly repeated polo-box domain (PBD) (in the case of Plk4, a tandem repeat of cryptic PBDs is found in the middle of the protein followed by a C-terminal single repeat), which appears to be involved in autoinhibition and in mediating the subcellular localization. The latter may be controlled via interactions between the polo-box domain and phospho-peptide motifs. The phosphopeptide binding site is formed at the interface between the two tandemly repeated PBDs. The PBDs of Plk4/Sak appear unique in participating in homodimer interactions, though it is not clear whether and how they interact with phosphopeptides [, , , , , ].In metazoans, Plk4 kinases control daughter centriole assembly. Plk4 homologues have an N-terminal kinase domain, a C-terminal polo box, and a central domain termed the 'cryptic polo box' (CPB) that has been shown to dimerize, to be sufficient for centriole localization and to be required for Plk4 to promote centriole assembly. Probable serine/threonine-protein kinase zyg-1 () (ZYG-1) is a Plk4 homologue found in C. elegans. Crystal structure for the CPB of C. elegans ZYG-1, reveals that it forms a Z-shaped dimer containing an intermolecular β-sheet with an extended basic surface patch. Electrostatic interactions between the basic patch on the ZYG-1 CPB dimer and the SPD-2 acidic region dock ZYG-1 onto centrioles to promote new centriole assembly. ZYG-1 CPB contains two tandem polo boxes (PB1 and PB2), each containing a six-stranded β-sheet with an α-helix packed against one side [].This entry represents the first (cryptic) polo-box domain of Plk4 and homologues.
Centriole amplification is controlled by two duplicated genes, Cep63 (centrosomal protein of 63kDa) and Deup1 (Deuterosome assembly protein 1).Cep63 regulates mother-centriole-dependent centriole duplication, whereas Deup1 is involved in large-scale de novo centriole biogenesis. Deup1, previously known as coiled-coil domain-containing protein 67, is a structural component of the deuterosome, a structure that promotes de novo centriole amplification in multiciliated cells. Deup1 binds to Cep152 and then recruits Plk4 to activate centriole biogenesis [].
This entry includes Cep85 and Cep85L from animals.Cep85 is a centrosomal protein of 85kDa []. It is a centriole duplication factor that directly interacts with STIL. It is essential for efficient centriolar targeting of STIL, PLK4 activation and faithful daughter centriole assembly [].Centrosomal protein of 85kDa-like (CEP85L) may localise to the centrosome []. It is also known as breast cancer antigen NY-BR-15 []. A chromosomal aberration involving CEP85L was found in a patient with T-lymphoblastic lymphoma and associated myeloproliferative neoplasm [].
This is the N-terminal domain found in components of the gamma-tubulin complex proteins (GCPs). Proteins containing this domain include spindle pole body (SBP) components such as Spc97 and Spc98 which function as the microtubule-organizing centre in yeast []. Proteins containing this domain also include human GCP4 (Gamma-tubulin complex component 4), which has been structurally elucidated []. Functional studies have shown that the N-terminal domain defines the functional identity of GCPs, suggesting that all GCPs are incorporated into the helix of gamma-tubulin small complexes (gTURCs) via lateral interactions between their N-terminal domains. Thereby, they define the direct neighbours and position the GCPs within the helical wall of gTuRC []. Sequence alignment of human GCPs based on the GCP4 structure helped delineate conserved regions in the N- and C-terminal domains []. In addition to the conserved sequences, the N-terminal domains carry specific insertions of various sizes depending on the GCP, i.e. internal insertions or N-terminal extensions. These insertions may equally contribute to the function of individual GCPs as they have been implied in specific interactions with regulatory or structural proteins. For instance, GCP6 carries a large internal insertion phosphorylated by Plk4 and containing a domain of interaction with keratins, whereas the N-terminal extension of GCP3 interacts with the recruitment protein MOZART1 [].
