Evidence map›Paper›PMID 32855301›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

The cryoelectron microscopy structure of the human CDK-activating kinase.

Basil J Greber, Juan M Perez-Bertoldi, Kif Lim, Anthony T Iavarone, Daniel B Toso, Eva Nogales

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
5.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Article
  3. Structural basis for P-TEFb association with BRD4.bioRxiv : the preprint server for biology · 2026
    Article
  4. Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026
    Review
  5. Article
  6. Article
  7. Article
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  9. Article
  10. Article
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  14. Review
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  19. Review
  20. Super enhancer lncRNAs: a novel hallmark in cancer.Cell communication and signaling : CCS · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Basil J GreberCalifornia Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720; basil.greber@icr.ac.uk ENogales@lbl.gov.
Juan M Perez-BertoldiBiophysics Graduate Group, University of California, Berkeley, CA 94720.ORCID 0000-0003-4590-820X
Kif LimDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720.
Anthony T IavaroneQB3/Chemistry Mass Spectrometry Facility, University of California, Berkeley, CA 94720.
Daniel B TosoCalifornia Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720.
Eva NogalesCalifornia Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720; basil.greber@icr.ac.uk ENogales@lbl.gov.ORCID 0000-0001-9816-3681
QB3 · USUniversity of California, Berkeley · US

Funding

PROJECT 5 - DUKE - STRUCTURE VALIDATION AND IMPROVEMENT FOR PROTEINS AND N. ACIDSP01GM063210 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI ADAMS, PAUL DAVID · 2001 to 2021
$33.5M
Structural studies of function and regulation of microtubules and transcriptional gene expression machineryR35GM127018 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Eva Nogales · 2018 to 2026
$4.3M
Structural Studies of the Eukaryotic Transcription Initiation MachineryR01GM063072 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI NOGALES, EVA · 2001 to 2016
$2.5M
High Definition Ion Mobility SpectrometerS10OD020062 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI WILLIAMS, EVAN R · 2015 to 2015
$590k
Howard Hughes Medical InstituteNIGMS NIH HHS P01 GM063210NIGMS NIH HHS R01 GM063072NIGMS NIH HHS R35 GM127018NIH HHS S10 OD020062
6 · The paper itself

Abstract

The human CDK-activating kinase (CAK), a complex composed of cyclin-dependent kinase (CDK) 7, cyclin H, and MAT1, is a critical regulator of transcription initiation and the cell cycle. It acts by phosphorylating the C-terminal heptapeptide repeat domain of the RNA polymerase II (Pol II) subunit RPB1, which is an important regulatory event in transcription initiation by Pol II, and it phosphorylates the regulatory T-loop of CDKs that control cell cycle progression. Here, we have determined the three-dimensional (3D) structure of the catalytic module of human CAK, revealing the structural basis of its assembly and providing insight into CDK7 activation in this context. The unique third component of the complex, MAT1, substantially extends the interaction interface between CDK7 and cyclin H, explaining its role as a CAK assembly factor, and it forms interactions with the CDK7 T-loop, which may contribute to enhancing CAK activity. We have also determined the structure of the CAK in complex with the covalently bound inhibitor THZ1 in order to provide insight into the binding of inhibitors at the CDK7 active site and to aid in the rational design of therapeutic compounds.

Indexed as

Cell CycleCell DivisionCryoelectron MicroscopyCyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesHumansPhosphorylationProtein Serine-Threonine KinasesRNA Polymerase IITranscription FactorsCDK7 protein, humanCyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesProtein Serine-Threonine KinasesRNA Polymerase IITranscription Factorscell cyclecryoelectron microscopycyclin-dependent kinasephosphorylationtranscription

Identifiers

PMID32855301
PMCPMC7502720
OpenAlexW3081150300

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.