1jfi

From Proteopedia

Jump to: navigation, search
1jfi, resolution 2.62Å ()
Gene: NC2 alpha (DRAP1) (Homo sapiens), NC2 beta (Dr1) (Homo sapiens), tbp (Homo sapiens)
Resources: FirstGlance, OCA, RCSB, PDBsum, TOPSAN
Coordinates: save as pdb, mmCIF, xml


Contents

Crystal Structure of the NC2-TBP-DNA Ternary Complex

Publication Abstract from PubMed

The X-ray structure of a ternary complex of Negative Cofactor 2 (NC2), the TATA box binding protein (TBP), and DNA has been determined at 2.6 A resolution. The N termini of NC2 alpha and beta resemble histones H2A and H2B, respectively, and form a heterodimer that binds to the bent DNA double helix on the underside of the preformed TBP-DNA complex via electrostatic interactions. NC2beta contributes to inhibition of TATA-dependent transcription through interactions of its C-terminal alpha helix with a conserved hydrophobic feature on the upper surface of TBP, which in turn positions the penultimate alpha helix of NC2beta to block recognition of the TBP-DNA complex by transcription factor IIB. Further regulatory implications of the NC2 heterodimer structure are discussed.

Crystal structure of negative cofactor 2 recognizing the TBP-DNA transcription complex., Kamada K, Shu F, Chen H, Malik S, Stelzer G, Roeder RG, Meisterernst M, Burley SK, Cell. 2001 Jul 13;106(1):71-81. PMID:11461703

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Disease

[TBP_HUMAN] Defects in TBP are the cause of spinocerebellar ataxia type 17 (SCA17) [MIM:607136]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA17 is an autosomal dominant cerebellar ataxia (ADCA) characterized by widespread cerebral and cerebellar atrophy, dementia and extrapyramidal signs. The molecular defect in SCA17 is the expansion of a CAG repeat in the coding region of TBP. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.[1][2][3]

Function

[NC2B_HUMAN] The association of the DR1/DRAP1 heterodimer with TBP results in a functional repression of both activated and basal transcription of class II genes. This interaction precludes the formation of a transcription-competent complex by inhibiting the association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its own. Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4.[4][5] [NC2A_HUMAN] The association of the DR1/DRAP1 heterodimer with TBP results in a functional repression of both activated and basal transcription of class II genes. This interaction precludes the formation of a transcription-competent complex by inhibiting the association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its own.[6][7] [TBP_HUMAN] General transcription factor that functions at the core of the DNA-binding multiprotein factor TFIID. Binding of TFIID to the TATA box is the initial transcriptional step of the pre-initiation complex (PIC), playing a role in the activation of eukaryotic genes transcribed by RNA polymerase II. Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1 with the rDNA promoter. SL1 is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA.[8]

About this Structure

1jfi is a 5 chain structure with sequence from Homo sapiens. The July 2005 RCSB PDB Molecule of the Month feature on TATA-Binding Protein by David S. Goodsell is 10.2210/rcsb_pdb/mom_2005_7. Full crystallographic information is available from OCA.

See Also

Reference

  • Kamada K, Shu F, Chen H, Malik S, Stelzer G, Roeder RG, Meisterernst M, Burley SK. Crystal structure of negative cofactor 2 recognizing the TBP-DNA transcription complex. Cell. 2001 Jul 13;106(1):71-81. PMID:11461703
  1. Zuhlke C, Hellenbroich Y, Dalski A, Kononowa N, Hagenah J, Vieregge P, Riess O, Klein C, Schwinger E. Different types of repeat expansion in the TATA-binding protein gene are associated with a new form of inherited ataxia. Eur J Hum Genet. 2001 Mar;9(3):160-4. PMID:11313753 doi:10.1038/sj.ejhg.5200617
  2. Nakamura K, Jeong SY, Uchihara T, Anno M, Nagashima K, Nagashima T, Ikeda S, Tsuji S, Kanazawa I. SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet. 2001 Jul 1;10(14):1441-8. PMID:11448935
  3. Silveira I, Miranda C, Guimaraes L, Moreira MC, Alonso I, Mendonca P, Ferro A, Pinto-Basto J, Coelho J, Ferreirinha F, Poirier J, Parreira E, Vale J, Januario C, Barbot C, Tuna A, Barros J, Koide R, Tsuji S, Holmes SE, Margolis RL, Jardim L, Pandolfo M, Coutinho P, Sequeiros J. Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus. Arch Neurol. 2002 Apr;59(4):623-9. PMID:11939898
  4. Goppelt A, Stelzer G, Lottspeich F, Meisterernst M. A mechanism for repression of class II gene transcription through specific binding of NC2 to TBP-promoter complexes via heterodimeric histone fold domains. EMBO J. 1996 Jun 17;15(12):3105-16. PMID:8670811
  5. Guelman S, Kozuka K, Mao Y, Pham V, Solloway MJ, Wang J, Wu J, Lill JR, Zha J. The double-histone-acetyltransferase complex ATAC is essential for mammalian development. Mol Cell Biol. 2009 Mar;29(5):1176-88. doi: 10.1128/MCB.01599-08. Epub 2008 Dec, 22. PMID:19103755 doi:10.1128/MCB.01599-08
  6. Goppelt A, Stelzer G, Lottspeich F, Meisterernst M. A mechanism for repression of class II gene transcription through specific binding of NC2 to TBP-promoter complexes via heterodimeric histone fold domains. EMBO J. 1996 Jun 17;15(12):3105-16. PMID:8670811
  7. Mermelstein F, Yeung K, Cao J, Inostroza JA, Erdjument-Bromage H, Eagelson K, Landsman D, Levitt P, Tempst P, Reinberg D. Requirement of a corepressor for Dr1-mediated repression of transcription. Genes Dev. 1996 Apr 15;10(8):1033-48. PMID:8608938
  8. Friedrich JK, Panov KI, Cabart P, Russell J, Zomerdijk JC. TBP-TAF complex SL1 directs RNA polymerase I pre-initiation complex formation and stabilizes upstream binding factor at the rDNA promoter. J Biol Chem. 2005 Aug 19;280(33):29551-8. Epub 2005 Jun 21. PMID:15970593 doi:10.1074/jbc.M501595200

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools