7BUL
Solution structure of the tandem PH and BSD1 domains of TFIIH p62
Summary for 7BUL
| Entry DOI | 10.2210/pdb7bul/pdb |
| NMR Information | BMRB: 36340 |
| Descriptor | General transcription factor IIH subunit 1 (1 entity in total) |
| Functional Keywords | dna repair factor, general transcription factor, nucleotide excision repair, nuclear protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 18348.99 |
| Authors | Okuda, M.,Nishimura, Y. (deposition date: 2020-04-07, release date: 2020-12-30, Last modification date: 2024-05-15) |
| Primary citation | Okuda, M.,Ekimoto, T.,Kurita, J.I.,Ikeguchi, M.,Nishimura, Y. Structural and dynamical insights into the PH domain of p62 in human TFIIH. Nucleic Acids Res., 49:2916-2930, 2021 Cited by PubMed Abstract: TFIIH is a crucial transcription and DNA repair factor consisting of the seven-subunit core. The core subunit p62 contains a pleckstrin homology domain (PH-D), which is essential for locating TFIIH at transcription initiation and DNA damage sites, and two BSD (BTF2-like transcription factors, synapse-associated proteins and DOS2-like proteins) domains. A recent cryo-electron microscopy (cryo-EM) structure of human TFIIH visualized most parts of core, except for the PH-D. Here, by nuclear magnetic resonance spectroscopy we have established the solution structure of human p62 PH-D connected to the BSD1 domain by a highly flexible linker, suggesting the flexibility of PH-D in TFIIH. Based on this dynamic character, the PH-D was modeled in the cryo-EM structure to obtain the whole human TFIIH core structure, which indicates that the PH-D moves around the surface of core with a specific but limited spatial distribution; these dynamic structures were refined by molecular dynamics (MD) simulations. Furthermore, we built models, also refined by MD simulations, of TFIIH in complex with five p62-binding partners, including transcription factors TFIIEα, p53 and DP1, and nucleotide excision repair factors XPC and UVSSA. The models explain why the PH-D is crucially targeted by these factors, which use their intrinsically disordered acidic regions for TFIIH recruitment. PubMed: 33211877DOI: 10.1093/nar/gkaa1045 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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