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Open data
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Basic information
Entry | Database: PDB / ID: 7kpv | ||||||
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Title | Structure of kinase and Central lobes of yeast CKM | ||||||
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Function / homology | ![]() negative regulation of filamentous growth / positive regulation of transcription by galactose / CKM complex / nuclear-transcribed mRNA catabolic process, non-stop decay / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
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![]() | Li, Y.C. / Chao, T.C. / Kim, H.J. / Cholko, T. / Chen, S.F. / Nakanishi, K. / Chang, C.E. / Murakami, K. / Garcia, B.A. / Boyer, T.G. / Tsai, K.L. | ||||||
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![]() | ![]() Title: Structure and noncanonical Cdk8 activation mechanism within an Argonaute-containing Mediator kinase module. Authors: Yi-Chuan Li / Ti-Chun Chao / Hee Jong Kim / Timothy Cholko / Shin-Fu Chen / Guojie Li / Laura Snyder / Kotaro Nakanishi / Chia-En Chang / Kenji Murakami / Benjamin A Garcia / Thomas G Boyer / Kuang-Lei Tsai / ![]() Abstract: 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 ...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 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. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 404.2 KB | Display | ![]() |
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PDB format | ![]() | 305 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 22989MC ![]() 7kpwC ![]() 7kpxC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 62940.906 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: ATCC 204508 / S288c References: UniProt: P39073, ![]() |
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#2: Protein | ![]() Mass: 37834.598 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: ATCC 204508 / S288c / References: UniProt: P47821 |
#3: Protein | Mass: 167049.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: ATCC 204508 / S288c / References: UniProt: P25648 |
#4: Protein | Mass: 160175.156 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: ATCC 204508 / S288c / References: UniProt: P38931 |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: yeast CDK8 complex![]() |
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Molecular weight | Value: 0.43 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 7.4 / Details: 25 mM Hepes pH 7.4, 200 mM NaCl, and 0.005% NP-40 |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Specimen support | Details: unspecified |
Vitrification![]() | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 % |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Image recording | Electron dose: 65 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 31534 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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