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Coiled-coil coactivators play a structural role mediating interactions in hypoxia-inducible factor heterodimerization.

Guo Y, Scheuermann TH, Partch CL, Tomchick DR, Gardner KH
J Biol Chem 290 7707-21 (2015)
Cited: 22 times
EuropePMC logo PMID: 25627682

Abstract

The hypoxia-inducible factor complex (HIF-α·aryl hydrocarbon receptor nuclear translocator (ARNT)) requires association with several transcription coactivators for a successful cellular response to hypoxic stress. In addition to the conventional global transcription coactivator CREB-binding protein/p300 (CBP/p300) that binds to the HIF-α transactivation domain, a new group of transcription coactivators called the coiled-coil coactivators (CCCs) interact directly with the second PER-ARNT-SIM (PAS) domain of ARNT (ARNT PAS-B). These less studied transcription coactivators play essential roles in the HIF-dependent hypoxia response, and CCC misregulation is associated with several forms of cancer. To better understand CCC protein recruitment by the heterodimeric HIF transcription factor, we used x-ray crystallography, NMR spectroscopy, and biochemical methods to investigate the structure of the ARNT PAS-B domain in complex with the C-terminal fragment of a coiled-coil coactivator protein, transforming acidic coiled-coil coactivator 3 (TACC3). We found that the HIF-2α PAS-B domain also directly interacts with TACC3, motivating an NMR data-derived model suggesting a means by which TACC3 could form a ternary complex with HIF-2α PAS-B and ARNT PAS-B via β-sheet/coiled-coil interactions. These findings suggest that TACC3 could be recruited as a bridge to cooperatively mediate between the HIF-2α PAS-B·ARNT PAS-B complex, thereby participating more directly in HIF-dependent gene transcription than previously anticipated.

Reviews - 4pky mentioned but not cited (2)

  1. Primase-polymerases are a functionally diverse superfamily of replication and repair enzymes. Guilliam TA, Keen BA, Brissett NC, Doherty AJ. Nucleic Acids Res 43 6651-6664 (2015)
  2. bHLH-PAS Proteins: Their Structure and Intrinsic Disorder. Kolonko M, Greb-Markiewicz B. Int J Mol Sci 20 E3653 (2019)

Articles - 4pky mentioned but not cited (3)

  1. Coiled-coil coactivators play a structural role mediating interactions in hypoxia-inducible factor heterodimerization. Guo Y, Scheuermann TH, Partch CL, Tomchick DR, Gardner KH. J Biol Chem 290 7707-7721 (2015)
  2. Hypoxia inducible factor (HIF) as a model for studying inhibition of protein-protein interactions. Burslem GM, Kyle HF, Nelson A, Edwards TA, Wilson AJ. Chem Sci 8 4188-4202 (2017)
  3. Erratum: Further Correction: Hypoxia inducible factor (HIF) as a model for studying inhibition of protein-protein interactions. Burslem GM, Kyle HF, Nelson A, Edwards TA, Wilson AJ. Chem Sci 9 2008-2009 (2018)


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  1. FGFR-TACC gene fusions in human glioma. Lasorella A, Sanson M, Iavarone A. Neuro Oncol 19 475-483 (2017)
  2. Exploring the developmental mechanisms underlying Wolf-Hirschhorn Syndrome: Evidence for defects in neural crest cell migration. Rutherford EL, Lowery LA. Dev Biol 420 1-10 (2016)

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  1. Structural integration in hypoxia-inducible factors. Wu D, Potluri N, Lu J, Kim Y, Rastinejad F. Nature 524 303-308 (2015)
  2. The myosin mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations. Nag S, Trivedi DV, Sarkar SS, Adhikari AS, Sunitha MS, Sutton S, Ruppel KM, Spudich JA. Nat Struct Mol Biol 24 525-533 (2017)
  3. Modulation of HIF-2α PAS-B domain contributes to physiological responses. Feng Z, Zou X, Chen Y, Wang H, Duan Y, Bruick RK. Proc Natl Acad Sci U S A 115 13240-13245 (2018)
  4. A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis. Li F, Cai Y, Deng S, Yang L, Liu N, Chang X, Jing L, Zhou Y, Li H. J Biol Chem 297 101182 (2021)
  5. FGFR3-TACC3 cancer gene fusions cause mitotic defects by removal of endogenous TACC3 from the mitotic spindle. Sarkar S, Ryan EL, Royle SJ. Open Biol 7 170080 (2017)
  6. Circadian clock mechanism driving mammalian photoperiodism. Wood SH, Hindle MM, Mizoro Y, Cheng Y, Saer BRC, Miedzinska K, Christian HC, Begley N, McNeilly J, McNeilly AS, Meddle SL, Burt DW, Loudon ASI. Nat Commun 11 4291 (2020)
  7. Molecular analysis of NPAS3 functional domains and variants. Luoma LM, Berry FB. BMC Mol Biol 19 14 (2018)
  8. TACC3 transcriptionally upregulates E2F1 to promote cell growth and confer sensitivity to cisplatin in bladder cancer. Lin ZR, Wang MY, He SY, Cai ZM, Huang WR. Cell Death Dis 9 72 (2018)
  9. Volume and compressibility differences between protein conformations revealed by high-pressure NMR. Xu X, Gagné D, Aramini JM, Gardner KH. Biophys J 120 924-935 (2021)
  10. Molecular convergent and parallel evolution among four high-elevation anuran species from the Tibetan region. Lu B, Jin H, Fu J. BMC Genomics 21 839 (2020)
  11. Druggability assessment of mammalian Per-Arnt-Sim [PAS] domains using computational approaches. de Souza JV, Reznikov S, Zhu R, Bronowska AK. Medchemcomm 10 1126-1137 (2019)
  12. NMR insight into myosin-binding subunit coiled-coil structure reveals binding interface with protein kinase G-Iα leucine zipper in vascular function. Sharma AK, Birrane G, Anklin C, Rigby AC, Alper SL. J Biol Chem 292 7052-7065 (2017)
  13. Fetal growth restriction: associated genetic etiology and pregnancy outcomes in a tertiary referral center. Cai M, Lin N, Su L, Wu X, Xie X, Xu S, Fu X, Xu L, Huang H. J Transl Med 20 168 (2022)
  14. Fragile protein folds: Sequence and environmental factors affecting the equilibrium of two interconverting, stably folded protein conformations. Xu X, Dikiy I, Evans MR, Marcelino LP, Gardner KH. Magn Reson (Gott) 2 63-76 (2021)
  15. Rare FGFR fusion genes in cervical cancer and transcriptome-based subgrouping of patients with a poor prognosis. Hiranuma K, Asami Y, Kato MK, Murakami N, Shimada Y, Matsuda M, Yazaki S, Fujii E, Sudo K, Kuno I, Komatsu M, Hamamoto R, Makinoshima H, Matsumoto K, Ishikawa M, Kohno T, Terao Y, Itakura A, Yoshida H, Shiraishi K, Kato T. Cancer Med 12 17835-17848 (2023)


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