Conserved Region I of Human Coactivator TAF4 Binds to a Short Hydrophobic Motif Present in Transcriptional Regulators

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 May 8

PMID 17483474

Citations 28

Authors

Xiaoping Wang

Dagmar M Truckses

Shinako Takada

Tatsushi Matsumura

Naoko Tanese

Raymond H Jacobson

Affiliations

Soon will be listed here.

Abstract

TBP-associated factor 4 (TAF4), an essential subunit of the TFIID complex acts as a coactivator for multiple transcriptional regulators, including Sp1 and CREB. However, little is known regarding the structural properties of the TAF4 subunit that lead to the coactivator function. Here, we report the crystal structure at 2.0-A resolution of the human TAF4-TAFH domain, a conserved domain among all metazoan TAF4, TAF4b, and ETO family members. The hTAF4-TAFH structure adopts a completely helical fold with a large hydrophobic groove that forms a binding surface for TAF4 interacting factors. Using peptide phage display, we have characterized the binding preference of the hTAF4-TAFH domain for a hydrophobic motif, DPsiPsizetazetaPsiPhi, that is present in a number of nuclear factors, including several important transcriptional regulators with roles in activating, repressing, and modulating posttranslational modifications. A comparison of the hTAF4-TAFH structure with the homologous ETO-TAFH domain reveals several critical residues important for hTAF4-TAFH target specificity and suggests that TAF4 has evolved in response to the increased transcriptional complexity of metazoans.

Citing Articles

Interaction modules that impart specificity to disordered protein.

Cermakova K, Hodges H Trends Biochem Sci. 2023; 48(5):477-490.

PMID: 36754681 PMC: 10106370. DOI: 10.1016/j.tibs.2023.01.004.

De novo putative loss-of-function variants in TAF4 are associated with a neuro-developmental disorder.

Janssen B, van den Boogaard M, Lichtenbelt K, Seaby E, Stals K, Ellard S Hum Mutat. 2022; 43(12):1844-1851.

PMID: 35904126 PMC: 10087332. DOI: 10.1002/humu.24444.

αα-hub coregulator structure and flexibility determine transcription factor binding and selection in regulatory interactomes.

Theisen F, Salladini E, Davidsen R, Rasmussen C, Staby L, Kragelund B J Biol Chem. 2022; 298(6):101963.

PMID: 35452682 PMC: 9127584. DOI: 10.1016/j.jbc.2022.101963.

What do Transcription Factors Interact With?.

Chen H, Pugh B J Mol Biol. 2021; 433(14):166883.

PMID: 33621520 PMC: 8184585. DOI: 10.1016/j.jmb.2021.166883.

αα-Hub domains and intrinsically disordered proteins: A decisive combo.

Bugge K, Staby L, Salladini E, Falbe-Hansen R, Kragelund B, Skriver K J Biol Chem. 2020; 296:100226.

PMID: 33361159 PMC: 7948954. DOI: 10.1074/jbc.REV120.012928.

References

Jacobson R, Ladurner A, King D, Tjian R . Structure and function of a human TAFII250 double bromodomain module. Science. 2000; 288(5470):1422-5. DOI: 10.1126/science.288.5470.1422. View

Wysocka J, Herr W . The herpes simplex virus VP16-induced complex: the makings of a regulatory switch. Trends Biochem Sci. 2003; 28(6):294-304. DOI: 10.1016/S0968-0004(03)00088-4. View

Murshudov G, Vagin A, Dodson E . Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr. 1997; 53(Pt 3):240-55. DOI: 10.1107/S0907444996012255. View

Mizzen C, Yang X, Kokubo T, Brownell J, Bannister A, Owen-Hughes T . The TAF(II)250 subunit of TFIID has histone acetyltransferase activity. Cell. 1996; 87(7):1261-70. DOI: 10.1016/s0092-8674(00)81821-8. View

Luciano R, Wilson A . N-terminal transcriptional activation domain of LZIP comprises two LxxLL motifs and the host cell factor-1 binding motif. Proc Natl Acad Sci U S A. 2000; 97(20):10757-62. PMC: 27096. DOI: 10.1073/pnas.190062797. View

Holton J, Alber T . Automated protein crystal structure determination using ELVES. Proc Natl Acad Sci U S A. 2004; 101(6):1537-42. PMC: 341770. DOI: 10.1073/pnas.0306241101. View

Davis J, McGhee L, Meyers S . The ETO (MTG8) gene family. Gene. 2003; 303:1-10. DOI: 10.1016/s0378-1119(02)01172-1. View

Plevin M, Zhang J, Guo C, Roeder R, Ikura M . The acute myeloid leukemia fusion protein AML1-ETO targets E proteins via a paired amphipathic helix-like TBP-associated factor homology domain. Proc Natl Acad Sci U S A. 2006; 103(27):10242-10247. PMC: 1502442. DOI: 10.1073/pnas.0603463103. View

Wright K, Marr 2nd M, Tjian R . TAF4 nucleates a core subcomplex of TFIID and mediates activated transcription from a TATA-less promoter. Proc Natl Acad Sci U S A. 2006; 103(33):12347-52. PMC: 1567882. DOI: 10.1073/pnas.0605499103. View

10.

Gattiker A, Gasteiger E, Bairoch A . ScanProsite: a reference implementation of a PROSITE scanning tool. Appl Bioinformatics. 2004; 1(2):107-8. View

11.

Cowtan K, Main P . Phase combination and cross validation in iterated density-modification calculations. Acta Crystallogr D Biol Crystallogr. 1996; 52(Pt 1):43-8. DOI: 10.1107/S090744499500761X. View

12.

Saluja D, Vassallo M, Tanese N . Distinct subdomains of human TAFII130 are required for interactions with glutamine-rich transcriptional activators. Mol Cell Biol. 1998; 18(10):5734-43. PMC: 109159. DOI: 10.1128/MCB.18.10.5734. View

13.

Shen W, Bhaumik S, Causton H, Simon I, Zhu X, Jennings E . Systematic analysis of essential yeast TAFs in genome-wide transcription and preinitiation complex assembly. EMBO J. 2003; 22(13):3395-402. PMC: 165660. DOI: 10.1093/emboj/cdg336. View

14.

Aasland R, Abrams C, Ampe C, Ball L, Bedford M, Cesareni G . Normalization of nomenclature for peptide motifs as ligands of modular protein domains. FEBS Lett. 2002; 513(1):141-4. DOI: 10.1016/s0014-5793(01)03295-1. View

15.

Zhou J, Zwicker J, Szymanski P, Levine M, Tjian R . TAFII mutations disrupt Dorsal activation in the Drosophila embryo. Proc Natl Acad Sci U S A. 1998; 95(23):13483-8. PMC: 24845. DOI: 10.1073/pnas.95.23.13483. View

16.

Mengus G, May M, Carre L, Chambon P, Davidson I . Human TAF(II)135 potentiates transcriptional activation by the AF-2s of the retinoic acid, vitamin D3, and thyroid hormone receptors in mammalian cells. Genes Dev. 1997; 11(11):1381-95. DOI: 10.1101/gad.11.11.1381. View

17.

Furukawa T, Tanese N . Assembly of partial TFIID complexes in mammalian cells reveals distinct activities associated with individual TATA box-binding protein-associated factors. J Biol Chem. 2000; 275(38):29847-56. DOI: 10.1074/jbc.M002989200. View

18.

Tora L . A unified nomenclature for TATA box binding protein (TBP)-associated factors (TAFs) involved in RNA polymerase II transcription. Genes Dev. 2002; 16(6):673-5. DOI: 10.1101/gad.976402. View

19.

Dunah A, Jeong H, Griffin A, Kim Y, Standaert D, Hersch S . Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science. 2002; 296(5576):2238-43. DOI: 10.1126/science.1072613. View

20.

Gangloff Y, Werten S, Romier C, Carre L, Poch O, Moras D . The human TFIID components TAF(II)135 and TAF(II)20 and the yeast SAGA components ADA1 and TAF(II)68 heterodimerize to form histone-like pairs. Mol Cell Biol. 1999; 20(1):340-51. PMC: 85089. DOI: 10.1128/MCB.20.1.340-351.2000. View