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. 2000 Sep;9(9):1743–1752. doi: 10.1110/ps.9.9.1743

Structure of a (Cys3His) zinc ribbon, a ubiquitous motif in archaeal and eucaryal transcription.

H T Chen 1, P Legault 1, J Glushka 1, J G Omichinski 1, R A Scott 1
PMCID: PMC2144703  PMID: 11045620

Abstract

Transcription factor IIB (TFIIB) is an essential component in the formation of the transcription initiation complex in eucaryal and archaeal transcription. TFIIB interacts with a promoter complex containing the TATA-binding protein (TBP) to facilitate interaction with RNA polymerase II (RNA pol II) and the associated transcription factor IIF (TFIIF). TFIIB contains a zinc-binding motif near the N-terminus that is directly involved in the interaction with RNA pol II/TFIIF and plays a crucial role in selecting the transcription initiation site. The solution structure of the N-terminal residues 2-59 of human TFIIB was determined by multidimensional NMR spectroscopy. The structure consists of a nearly tetrahedral Zn(Cys)3(His)1 site confined by type I and "rubredoxin" turns, three antiparallel beta-strands, and disordered loops. The structure is similar to the reported zinc-ribbon motifs in several transcription-related proteins from archaea and eucarya, including Pyrococcus furiosus transcription factor B (PfTFB), human and yeast transcription factor IIS (TFIIS), and Thermococcus celer RNA polymerase II subunit M (TcRPOM). The zinc-ribbon structure of TFIIB, in conjunction with the biochemical analyses, suggests that residues on the beta-sheet are involved in the interaction with RNA pol II/TFIIF, while the zinc-binding site may increase the stability of the beta-sheet.

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Selected References

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  1. Adman E., Watenpaugh K. D., Jensen L. H. NH---S hydrogen bonds in Peptococcus aerogenes ferredoxin, Clostridium pasteurianum rubredoxin, and Chromatium high potential iron protein. Proc Natl Acad Sci U S A. 1975 Dec;72(12):4854–4858. doi: 10.1073/pnas.72.12.4854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Agarwal K., Baek K. H., Jeon C. J., Miyamoto K., Ueno A., Yoon H. S. Stimulation of transcript elongation requires both the zinc finger and RNA polymerase II binding domains of human TFIIS. Biochemistry. 1991 Aug 6;30(31):7842–7851. doi: 10.1021/bi00245a026. [DOI] [PubMed] [Google Scholar]
  3. Bagby S., Kim S., Maldonado E., Tong K. I., Reinberg D., Ikura M. Solution structure of the C-terminal core domain of human TFIIB: similarity to cyclin A and interaction with TATA-binding protein. Cell. 1995 Sep 8;82(5):857–867. doi: 10.1016/0092-8674(95)90483-2. [DOI] [PubMed] [Google Scholar]
  4. Baker E. N., Hubbard R. E. Hydrogen bonding in globular proteins. Prog Biophys Mol Biol. 1984;44(2):97–179. doi: 10.1016/0079-6107(84)90007-5. [DOI] [PubMed] [Google Scholar]
  5. Bangur C. S., Pardee T. S., Ponticelli A. S. Mutational analysis of the D1/E1 core helices and the conserved N-terminal region of yeast transcription factor IIB (TFIIB): identification of an N-terminal mutant that stabilizes TATA-binding protein-TFIIB-DNA complexes. Mol Cell Biol. 1997 Dec;17(12):6784–6793. doi: 10.1128/mcb.17.12.6784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barberis A., Müller C. W., Harrison S. C., Ptashne M. Delineation of two functional regions of transcription factor TFIIB. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5628–5632. doi: 10.1073/pnas.90.12.5628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brünger A. T., Adams P. D., Clore G. M., DeLano W. L., Gros P., Grosse-Kunstleve R. W., Jiang J. S., Kuszewski J., Nilges M., Pannu N. S. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905–921. doi: 10.1107/s0907444998003254. [DOI] [PubMed] [Google Scholar]
  8. Bult C. J., White O., Olsen G. J., Zhou L., Fleischmann R. D., Sutton G. G., Blake J. A., FitzGerald L. M., Clayton R. A., Gocayne J. D. Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii. Science. 1996 Aug 23;273(5278):1058–1073. doi: 10.1126/science.273.5278.1058. [DOI] [PubMed] [Google Scholar]
  9. Buratowski S., Zhou H. Functional domains of transcription factor TFIIB. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5633–5637. doi: 10.1073/pnas.90.12.5633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bushnell D. A., Bamdad C., Kornberg R. D. A minimal set of RNA polymerase II transcription protein interactions. J Biol Chem. 1996 Aug 16;271(33):20170–20174. doi: 10.1074/jbc.271.33.20170. [DOI] [PubMed] [Google Scholar]
  11. Clore G. M., Gronenborn A. M. Determination of three-dimensional structures of proteins and nucleic acids in solution by nuclear magnetic resonance spectroscopy. Crit Rev Biochem Mol Biol. 1989;24(5):479–564. doi: 10.3109/10409238909086962. [DOI] [PubMed] [Google Scholar]
  12. Colangelo C. M., Lewis L. M., Cosper N. J., Scott R. A. Structural evidence for a common zinc binding domain in archaeal and eukaryal transcription factor IIB proteins. J Biol Inorg Chem. 2000 Apr;5(2):276–283. doi: 10.1007/s007750050372. [DOI] [PubMed] [Google Scholar]
  13. Cramer P., Bushnell D. A., Fu J., Gnatt A. L., Maier-Davis B., Thompson N. E., Burgess R. R., Edwards A. M., David P. R., Kornberg R. D. Architecture of RNA polymerase II and implications for the transcription mechanism. Science. 2000 Apr 28;288(5466):640–649. doi: 10.1126/science.288.5466.640. [DOI] [PubMed] [Google Scholar]
  14. Delaglio F., Grzesiek S., Vuister G. W., Zhu G., Pfeifer J., Bax A. NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR. 1995 Nov;6(3):277–293. doi: 10.1007/BF00197809. [DOI] [PubMed] [Google Scholar]
  15. Fang S. M., Burton Z. F. RNA polymerase II-associated protein (RAP) 74 binds transcription factor (TF) IIB and blocks TFIIB-RAP30 binding. J Biol Chem. 1996 May 17;271(20):11703–11709. doi: 10.1074/jbc.271.20.11703. [DOI] [PubMed] [Google Scholar]
  16. Fourmy D., Dardel F., Blanquet S. Methionyl-tRNA synthetase zinc binding domain. Three-dimensional structure and homology with rubredoxin and gag retroviral proteins. J Mol Biol. 1993 Jun 20;231(4):1078–1089. doi: 10.1006/jmbi.1993.1353. [DOI] [PubMed] [Google Scholar]
  17. Ha I., Roberts S., Maldonado E., Sun X., Kim L. U., Green M., Reinberg D. Multiple functional domains of human transcription factor IIB: distinct interactions with two general transcription factors and RNA polymerase II. Genes Dev. 1993 Jun;7(6):1021–1032. doi: 10.1101/gad.7.6.1021. [DOI] [PubMed] [Google Scholar]
  18. Halkides C. J., Wu Y. Q., Murray C. J. A low-barrier hydrogen bond in subtilisin: 1H and 15N NMR studies with peptidyl trifluoromethyl ketones. Biochemistry. 1996 Dec 10;35(49):15941–15948. doi: 10.1021/bi961805f. [DOI] [PubMed] [Google Scholar]
  19. Hampsey M. Molecular genetics of the RNA polymerase II general transcriptional machinery. Microbiol Mol Biol Rev. 1998 Jun;62(2):465–503. doi: 10.1128/mmbr.62.2.465-503.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hawkes N. A., Roberts S. G. The role of human TFIIB in transcription start site selection in vitro and in vivo. J Biol Chem. 1999 May 14;274(20):14337–14343. doi: 10.1074/jbc.274.20.14337. [DOI] [PubMed] [Google Scholar]
  21. Hisatake K., Roeder R. G., Horikoshi M. Functional dissection of TFIIB domains required for TFIIB-TFIID-promoter complex formation and basal transcription activity. Nature. 1993 Jun 24;363(6431):744–747. doi: 10.1038/363744a0. [DOI] [PubMed] [Google Scholar]
  22. Koradi R., Billeter M., Wüthrich K. MOLMOL: a program for display and analysis of macromolecular structures. J Mol Graph. 1996 Feb;14(1):51-5, 29-32. doi: 10.1016/0263-7855(96)00009-4. [DOI] [PubMed] [Google Scholar]
  23. Kusakabe T., Hine A. V., Hyberts S. G., Richardson C. C. The Cys4 zinc finger of bacteriophage T7 primase in sequence-specific single-stranded DNA recognition. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4295–4300. doi: 10.1073/pnas.96.8.4295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Laskowski R. A., Rullmannn J. A., MacArthur M. W., Kaptein R., Thornton J. M. AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR. J Biomol NMR. 1996 Dec;8(4):477–486. doi: 10.1007/BF00228148. [DOI] [PubMed] [Google Scholar]
  25. Lin Y., Nomura T., Cheong J., Dorjsuren D., Iida K., Murakami S. Hepatitis B virus X protein is a transcriptional modulator that communicates with transcription factor IIB and the RNA polymerase II subunit 5. J Biol Chem. 1997 Mar 14;272(11):7132–7139. doi: 10.1074/jbc.272.11.7132. [DOI] [PubMed] [Google Scholar]
  26. Malik S., Lee D. K., Roeder R. G. Potential RNA polymerase II-induced interactions of transcription factor TFIIB. Mol Cell Biol. 1993 Oct;13(10):6253–6259. doi: 10.1128/mcb.13.10.6253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Marion D., Driscoll P. C., Kay L. E., Wingfield P. T., Bax A., Gronenborn A. M., Clore G. M. Overcoming the overlap problem in the assignment of 1H NMR spectra of larger proteins by use of three-dimensional heteronuclear 1H-15N Hartmann-Hahn-multiple quantum coherence and nuclear Overhauser-multiple quantum coherence spectroscopy: application to interleukin 1 beta. Biochemistry. 1989 Jul 25;28(15):6150–6156. doi: 10.1021/bi00441a004. [DOI] [PubMed] [Google Scholar]
  28. Myer V. E., Young R. A. RNA polymerase II holoenzymes and subcomplexes. J Biol Chem. 1998 Oct 23;273(43):27757–27760. doi: 10.1074/jbc.273.43.27757. [DOI] [PubMed] [Google Scholar]
  29. Nikolov D. B., Chen H., Halay E. D., Usheva A. A., Hisatake K., Lee D. K., Roeder R. G., Burley S. K. Crystal structure of a TFIIB-TBP-TATA-element ternary complex. Nature. 1995 Sep 14;377(6545):119–128. doi: 10.1038/377119a0. [DOI] [PubMed] [Google Scholar]
  30. Ohkuma Y., Sumimoto H., Hoffmann A., Shimasaki S., Horikoshi M., Roeder R. G. Structural motifs and potential sigma homologies in the large subunit of human general transcription factor TFIIE. Nature. 1991 Dec 5;354(6352):398–401. doi: 10.1038/354398a0. [DOI] [PubMed] [Google Scholar]
  31. Olmsted V. K., Awrey D. E., Koth C., Shan X., Morin P. E., Kazanis S., Edwards A. M., Arrowsmith C. H. Yeast transcript elongation factor (TFIIS), structure and function. I: NMR structural analysis of the minimal transcriptionally active region. J Biol Chem. 1998 Aug 28;273(35):22589–22594. doi: 10.1074/jbc.273.35.22589. [DOI] [PubMed] [Google Scholar]
  32. Omichinski J. G., Clore G. M., Appella E., Sakaguchi K., Gronenborn A. M. High-resolution three-dimensional structure of a single zinc finger from a human enhancer binding protein in solution. Biochemistry. 1990 Oct 9;29(40):9324–9334. doi: 10.1021/bi00492a004. [DOI] [PubMed] [Google Scholar]
  33. Orphanides G., Lagrange T., Reinberg D. The general transcription factors of RNA polymerase II. Genes Dev. 1996 Nov 1;10(21):2657–2683. doi: 10.1101/gad.10.21.2657. [DOI] [PubMed] [Google Scholar]
  34. Pace C. N., Vajdos F., Fee L., Grimsley G., Gray T. How to measure and predict the molar absorption coefficient of a protein. Protein Sci. 1995 Nov;4(11):2411–2423. doi: 10.1002/pro.5560041120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pardee T. S., Bangur C. S., Ponticelli A. S. The N-terminal region of yeast TFIIB contains two adjacent functional domains involved in stable RNA polymerase II binding and transcription start site selection. J Biol Chem. 1998 Jul 10;273(28):17859–17864. doi: 10.1074/jbc.273.28.17859. [DOI] [PubMed] [Google Scholar]
  36. Peterson M. G., Inostroza J., Maxon M. E., Flores O., Admon A., Reinberg D., Tjian R. Structure and functional properties of human general transcription factor IIE. Nature. 1991 Dec 5;354(6352):369–373. doi: 10.1038/354369a0. [DOI] [PubMed] [Google Scholar]
  37. Pinto I., Ware D. E., Hampsey M. The yeast SUA7 gene encodes a homolog of human transcription factor TFIIB and is required for normal start site selection in vivo. Cell. 1992 Mar 6;68(5):977–988. doi: 10.1016/0092-8674(92)90040-j. [DOI] [PubMed] [Google Scholar]
  38. Pinto I., Wu W. H., Na J. G., Hampsey M. Characterization of sua7 mutations defines a domain of TFIIB involved in transcription start site selection in yeast. J Biol Chem. 1994 Dec 2;269(48):30569–30573. [PubMed] [Google Scholar]
  39. Pérez-Alvarado G. C., Miles C., Michelsen J. W., Louis H. A., Winge D. R., Beckerle M. C., Summers M. F. Structure of the carboxy-terminal LIM domain from the cysteine rich protein CRP. Nat Struct Biol. 1994 Jun;1(6):388–398. doi: 10.1038/nsb0694-388. [DOI] [PubMed] [Google Scholar]
  40. Qian X., Gozani S. N., Yoon H., Jeon C. J., Agarwal K., Weiss M. A. Novel zinc finger motif in the basal transcriptional machinery: three-dimensional NMR studies of the nucleic acid binding domain of transcriptional elongation factor TFIIS. Biochemistry. 1993 Sep 28;32(38):9944–9959. doi: 10.1021/bi00089a010. [DOI] [PubMed] [Google Scholar]
  41. Rance M., Sørensen O. W., Bodenhausen G., Wagner G., Ernst R. R., Wüthrich K. Improved spectral resolution in cosy 1H NMR spectra of proteins via double quantum filtering. Biochem Biophys Res Commun. 1983 Dec 16;117(2):479–485. doi: 10.1016/0006-291x(83)91225-1. [DOI] [PubMed] [Google Scholar]
  42. Rice L. M., Brünger A. T. Torsion angle dynamics: reduced variable conformational sampling enhances crystallographic structure refinement. Proteins. 1994 Aug;19(4):277–290. doi: 10.1002/prot.340190403. [DOI] [PubMed] [Google Scholar]
  43. Richardson J. S. The anatomy and taxonomy of protein structure. Adv Protein Chem. 1981;34:167–339. doi: 10.1016/s0065-3233(08)60520-3. [DOI] [PubMed] [Google Scholar]
  44. Roberts S. G., Green M. R. Activator-induced conformational change in general transcription factor TFIIB. Nature. 1994 Oct 20;371(6499):717–720. doi: 10.1038/371717a0. [DOI] [PubMed] [Google Scholar]
  45. Schwabe J. W., Klug A. Zinc mining for protein domains. Nat Struct Biol. 1994 Jun;1(6):345–349. doi: 10.1038/nsb0694-345. [DOI] [PubMed] [Google Scholar]
  46. Stein E. G., Rice L. M., Brünger A. T. Torsion-angle molecular dynamics as a new efficient tool for NMR structure calculation. J Magn Reson. 1997 Jan;124(1):154–164. doi: 10.1006/jmre.1996.1027. [DOI] [PubMed] [Google Scholar]
  47. Summers M. F., South T. L., Kim B., Hare D. R. High-resolution structure of an HIV zinc fingerlike domain via a new NMR-based distance geometry approach. Biochemistry. 1990 Jan 16;29(2):329–340. doi: 10.1021/bi00454a005. [DOI] [PubMed] [Google Scholar]
  48. Thomm M. Archaeal transcription factors and their role in transcription initiation. FEMS Microbiol Rev. 1996 May;18(2-3):159–171. doi: 10.1111/j.1574-6976.1996.tb00234.x. [DOI] [PubMed] [Google Scholar]
  49. Tschochner H., Sayre M. H., Flanagan P. M., Feaver W. J., Kornberg R. D. Yeast RNA polymerase II initiation factor e: isolation and identification as the functional counterpart of human transcription factor IIB. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11292–11296. doi: 10.1073/pnas.89.23.11292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wang B., Jones D. N., Kaine B. P., Weiss M. A. High-resolution structure of an archaeal zinc ribbon defines a general architectural motif in eukaryotic RNA polymerases. Structure. 1998 May 15;6(5):555–569. doi: 10.1016/s0969-2126(98)00058-6. [DOI] [PubMed] [Google Scholar]
  51. Watenpaugh K. D., Sieker L. C., Jensen L. H. Crystallographic refinement of rubredoxin at 1 x 2 A degrees resolution. J Mol Biol. 1980 Apr 15;138(3):615–633. doi: 10.1016/s0022-2836(80)80020-9. [DOI] [PubMed] [Google Scholar]
  52. Wu W. H., Hampsey M. An activation-specific role for transcription factor TFIIB in vivo. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2764–2769. doi: 10.1073/pnas.96.6.2764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Yamashita S., Hisatake K., Kokubo T., Doi K., Roeder R. G., Horikoshi M., Nakatani Y. Transcription factor TFIIB sites important for interaction with promoter-bound TFIID. Science. 1993 Jul 23;261(5120):463–466. doi: 10.1126/science.8332911. [DOI] [PubMed] [Google Scholar]
  54. Zhang O., Kay L. E., Olivier J. P., Forman-Kay J. D. Backbone 1H and 15N resonance assignments of the N-terminal SH3 domain of drk in folded and unfolded states using enhanced-sensitivity pulsed field gradient NMR techniques. J Biomol NMR. 1994 Nov;4(6):845–858. doi: 10.1007/BF00398413. [DOI] [PubMed] [Google Scholar]
  55. Zhu W., Zeng Q., Colangelo C. M., Lewis M., Summers M. F., Scott R. A. The N-terminal domain of TFIIB from Pyrococcus furiosus forms a zinc ribbon. Nat Struct Biol. 1996 Feb;3(2):122–124. doi: 10.1038/nsb0296-122. [DOI] [PubMed] [Google Scholar]

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