7kpv

Structure of kinase and Central lobes of yeast CKM

spinqualitylabelsall models 7kpv, resolution 3.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7kpv is a 4 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.8Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SSN3_YEAST Component of the SRB8-11 complex. The SRB8-11 complex is a regulatory module of the Mediator complex which is itself involved in regulation of basal and activated RNA polymerase II-dependent transcription. The SRB8-11 complex may be involved in the transcriptional repression of a subset of genes regulated by Mediator. It may inhibit the association of the Mediator complex with RNA polymerase II to form the holoenzyme complex. The SRB8-11 complex phosphorylates the C-terminal domain (CTD) of the largest subunit of RNA polymerase II RPB1 at serines 2 and 5. The SSN3/SRB10 and SSN8/SRB11 kinase-cyclin pair may also positively and negatively regulate numerous transcriptional activators in response to changes in nutritional and physiological conditions. Phosphorylates GCN4, promoting its ubiquitin-mediated degradation, and MSN2, promoting its nuclear exclusion. Phosphorylates STE12, thereby promoting its degradation and inhibition of filamentous growth. Phosphorylates GAL4, and this phosphorylation is required for efficient galactose-inducible transcription. Also phosphorylates BDF1 and the TAF2 subunit of the TFIID complex. Publication Abstract from PubMed The Cdk8 kinase module (CKM) in Mediator, comprising Med13, Med12, CycC, and Cdk8, regulates RNA polymerase II transcription through kinase-dependent and -independent functions. Numerous pathogenic mutations causative for neurodevelopmental disorders and cancer congregate in CKM subunits. However, the structure of the intact CKM and the mechanism by which Cdk8 is non-canonically activated and functionally affected by oncogenic CKM alterations are poorly understood. Here, we report a cryo-electron microscopy structure of Saccharomyces cerevisiae CKM that redefines prior CKM structural models and explains the mechanism of Med12-dependent Cdk8 activation. Med12 interacts extensively with CycC and activates Cdk8 by stabilizing its activation (T-)loop through conserved Med12 residues recurrently mutated in human tumors. Unexpectedly, Med13 has a characteristic Argonaute-like bi-lobal architecture. These findings not only provide a structural basis for understanding CKM function and pathological dysfunction, but also further impute a previously unknown regulatory mechanism of Mediator in transcriptional modulation through its Med13 Argonaute-like features. Structure and noncanonical Cdk8 activation mechanism within an Argonaute-containing Mediator kinase module.,Li YC, Chao TC, Kim HJ, Cholko T, Chen SF, Li G, Snyder L, Nakanishi K, Chang CE, Murakami K, Garcia BA, Boyer TG, Tsai KL Sci Adv. 2021 Jan 15;7(3):eabd4484. doi: 10.1126/sciadv.abd4484. Print 2021 Jan. PMID:33523904 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Mediator RNA polymerase 3D structures

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