5OF4

The cryo-EM structure of human TFIIH

Summary for 5OF4

• Entry DOI: 10.2210/pdb5of4/pdb
• EMDB information: 3802
• Descriptor: TFIIH basal transcription factor complex helicase XPB subunit,XPB,TFIIH basal transcription factor complex helicase XPB subunit, Unassigned secondary structure elements (XPB NTE region), IRON/SULFUR CLUSTER, ... (11 entities in total)
• Functional Keywords: transcription initiation, dna repair, multiprotein complex, kinase, helicase, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 306618.26

Authors

Greber, B.J.,Nguyen, T.H.D.,Fang, J.,Afonine, P.V.,Adams, P.D.,Nogales, E. (deposition date: 2017-07-10, release date: 2017-09-13, Last modification date: 2024-07-10)

Primary citation

Greber, B.J.,Nguyen, T.H.D.,Fang, J.,Afonine, P.V.,Adams, P.D.,Nogales, E.
The cryo-electron microscopy structure of human transcription factor IIH.
Nature, 549:414-417, 2017

PubMed Abstract: Human transcription factor IIH (TFIIH) is part of the general transcriptional machinery required by RNA polymerase II for the initiation of eukaryotic gene transcription. Composed of ten subunits that add up to a molecular mass of about 500 kDa, TFIIH is also essential for nucleotide excision repair. The seven-subunit TFIIH core complex formed by XPB, XPD, p62, p52, p44, p34, and p8 is competent for DNA repair, while the CDK-activating kinase subcomplex, which includes the kinase activity of CDK7 as well as the cyclin H and MAT1 subunits, is additionally required for transcription initiation. Mutations in the TFIIH subunits XPB, XPD, and p8 lead to severe premature ageing and cancer propensity in the genetic diseases xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy, highlighting the importance of TFIIH for cellular physiology. Here we present the cryo-electron microscopy structure of human TFIIH at 4.4 Å resolution. The structure reveals the molecular architecture of the TFIIH core complex, the detailed structures of its constituent XPB and XPD ATPases, and how the core and kinase subcomplexes of TFIIH are connected. Additionally, our structure provides insight into the conformational dynamics of TFIIH and the regulation of its activity.

PubMed: 28902838
DOI: 10.1038/nature23903

Experimental method

ELECTRON MICROSCOPY (4.4 Å)