4xb0 | pdb_00004xb0
Structure of the Plk2 polo-box domain
Structural highlights
FunctionPLK2_HUMAN Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress.[1] [2] [3] [4] Publication Abstract from PubMedPolo-like kinases (Plks) are the key regulators of cell cycle progression, the members of which share a kinase domain and a polo-box domain (PBD) that serves as a protein-binding module. While Plk1 is a promising target for antitumor therapy, Plk2 is regarded as a tumor suppressor even though the two Plks commonly recognize the S-pS/T-P motif through their PBD. Herein, we report the crystal structure of the PBD of Plk2 at 2.7 A. Despite the overall structural similarity with that of Plk1 reflecting their high sequence homology, the crystal structure also contains its own features including the highly ordered loop connecting two subdomains and the absence of 310 -helices in the N-terminal region unlike the PBD of Plk1. Based on the three-dimensional structure, we furthermore could model its interaction with two types of phosphopeptides, one of which was previously screened as the optimal peptide for the PBD of Plk2. Proteins 2015. (c) 2015 Wiley Periodicals, Inc. Structural analysis of the polo-box domain of human Polo-like kinase 2.,Kim JH, Ku B, Lee KS, Kim SJ Proteins. 2015 Apr 3. doi: 10.1002/prot.24804. PMID:25846005[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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