4zdr

Crystal structure of 14-3-3[zeta]-LKB1 fusion protein

spinqualitylabelsall models 4zdr, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4zdr is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.899Å Ligands: GOL, SO4, TME Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease STK11_HUMAN Defects in STK11 are a cause of Peutz-Jeghers syndrome (PJS) [MIM:175200. PJS is a rare hereditary disease in which there is predisposition to benign and malignant tumors of many organ systems. PJS is an autosomal dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer. Defects in STK11 have been associated with testicular germ cell tumor (TGCT) [MIM:273300. A common solid malignancy in males. Germ cell tumors of the testis constitute 95% of all testicular neoplasms. Note=Defects in STK11 are associated with some sporadic cancers, especially lung cancers. Frequently mutated and inactivated in non-small cell lung cancer (NSCLC). Defects promote lung cancerigenesis process, especially lung cancer progression and metastasis. Confers lung adenocarcinoma the ability to trans-differentiate into squamous cell carcinoma. Also able to promotes lung cancer metastasis, via both cancer-cell autonomous and non-cancer-cell autonomous mechanisms. Function 1433Z_HUMAN Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. STK11_HUMAN Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, leading to promote their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2: it thereby regulates inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neurons polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1 Also acts as a mediator p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. Publication Abstract from PubMed The 14-3-3 proteins are a family of highly conserved proteins that play key roles in many cellular processes. The tumour suppressor LKB1 regulates cell polarity, cell growth and energy metabolism. 14-3-3 proteins bind to LKB1 and suppress its functions. Previously, preliminary crystallographic data for the 14-3-3zeta-LKB1 fusion protein have been reported. Here, the crystal structure of this fusion protein was solved and a novel potential binding mode of 14-3-3 to its ligands was found. Structure of the 14-3-3zeta-LKB1 fusion protein provides insight into a novel ligand-binding mode of 14-3-3.,Ding S, Zhou R, Zhu Y Acta Crystallogr F Struct Biol Commun. 2015 Sep;71(Pt 9):1114-9. doi:, 10.1107/S2053230X15012595. Epub 2015 Aug 25. PMID:26323294 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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