6O9M

Structure of the human apo TFIIH

Summary for 6O9M

• Entry DOI: 10.2210/pdb6o9m/pdb
• EMDB information: 3802
• Descriptor: TFIIH basal transcription factor complex helicase XPD subunit, ZINC ION, General transcription factor IIH subunit 1, ... (10 entities in total)
• Functional Keywords: transcription initiation, molecular dynamics, gene regulation, community network analysis, global protein dynamics, rna polymerase, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 414363.89

Authors

Yan, C.L.,Dodd, T.,He, Y.,Tainer, J.A.,Tsutakawa, S.E.,Ivanov, I. (deposition date: 2019-03-14, release date: 2019-05-29, Last modification date: 2024-03-13)

Primary citation

Yan, C.,Dodd, T.,He, Y.,Tainer, J.A.,Tsutakawa, S.E.,Ivanov, I.
Transcription preinitiation complex structure and dynamics provide insight into genetic diseases.
Nat.Struct.Mol.Biol., 26:397-406, 2019

PubMed Abstract: Transcription preinitiation complexes (PICs) are vital assemblies whose function underlies the expression of protein-encoding genes. Cryo-EM advances have begun to uncover their structural organization. Nevertheless, functional analyses are hindered by incompletely modeled regions. Here we integrate all available cryo-EM data to build a practically complete human PIC structural model. This enables simulations that reveal the assembly's global motions, define PIC partitioning into dynamic communities and delineate how structural modules function together to remodel DNA. We identify key TFIIE-p62 interactions that link core-PIC to TFIIH. p62 rigging interlaces p34, p44 and XPD while capping the DNA-binding and ATP-binding sites of XPD. PIC kinks and locks substrate DNA, creating negative supercoiling within the Pol II cleft to facilitate promoter opening. Mapping disease mutations associated with xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome onto defined communities reveals clustering into three mechanistic classes that affect TFIIH helicase functions, protein interactions and interface dynamics.

PubMed: 31110295
DOI: 10.1038/s41594-019-0220-3

Experimental method

ELECTRON MICROSCOPY (4.4 Å)