6mzd | pdb_00006mzd
Human TFIID Lobe A canonical
Structural highlights
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] [TAF1_HUMAN] Defects in TAF1 are the cause of dystonia type 3 (DYT3) [MIM:314250]; also called X-linked dystonia-parkinsonism (XDP). DYT3 is a X-linked dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT3 is characterized by severe progressive torsion dystonia followed by parkinsonism. Its prevalence is high in the Philippines. DYT3 has a well-defined pathology of extensive neuronal loss and mosaic gliosis in the striatum (caudate nucleus and putamen) which appears to resemble that in Huntington disease.[4] [5] Function[TAF9_HUMAN] Essential for cell viability. TAF9 and TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes. May have a role in gene regulation associated with apoptosis. TAFs are components of the transcription factor IID (TFIID) complex, the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. TFIID or TFTC are essential for the regulation of RNA polymerase II-mediated transcription.[6] [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.[7] [TAF4_HUMAN] Makes part of TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. Potentiates transcriptional activation by the AF-2S of the retinoic acid, vitamin D3 and thyroid hormone. [TAF10_HUMAN] TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TIIFD is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. [TAF12_HUMAN] TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TAFs components-TIIFD are essential for mediating regulation of RNA polymerase transcription. [TAF3_HUMAN] Transcription factor TFIID is one of the general factors required for accurate and regulated initiation by RNA polymerase II. TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. Required in complex with TBPL2 for the differentiation of myoblasts into myocytes. The complex replaces TFIID at specific promoters at an early stage in the differentiation process. [TAF11_HUMAN] Core TAFII present in both of the previously described TFIID species which either lack or contain TAFII30 (TFIID alpha and TFIID beta respectively). [TAF5_HUMAN] TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TAFs components-TIIFD are essential for mediating regulation of RNA polymerase transcription. TAF5/TAFII100 interacts strongly with the histone H4-related TAF6/TAFII80 and the histone H3-related TAF9/TAFII31, as well as a stable complex comprised of both TAF5/TAFII80 and TAF6/TAFII31. Apparently weaker interactions of TAF5/TAFII100 with TBP, TAF1/TAFII250, TAF11/TAFII28, and TAF12/TAFII20, but not TAF7/TAFII55, also have been observed. [TAF1_HUMAN] Largest component and core scaffold of the TFIID basal transcription factor complex. Contains novel N- and C-terminal Ser/Thr kinase domains which can autophosphorylate or transphosphorylate other transcription factors. Phosphorylates TP53 on 'Thr-55' which leads to MDM2-mediated degradation of TP53. Phosphorylates GTF2A1 and GTF2F1 on Ser residues. Possesses DNA-binding activity. Essential for progression of the G1 phase of the cell cycle.[8] [9] [10] [11] [12] [13] [14] [TAF13_HUMAN] TFIID beta-specific TAFII. [TAF6_HUMAN] TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TIIFD is multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. Publication Abstract from PubMedThe general transcription factor IID (TFIID) is a critical component of the eukaryotic transcription preinitiation complex (PIC) and is responsible for recognizing the core promoter DNA and initiating PIC assembly. We used cryo-electron microscopy (cryo-EM), chemical crosslinking-mass spectrometry (CX-MS) and biochemical reconstitution to determine the complete molecular architecture of TFIID and define the conformational landscape of TFIID in the process of TATA-box binding protein (TBP) loading onto promoter DNA. Our structural analysis revealed five structural states of TFIID in the presence of TFIIA and promoter DNA, showing that the initial binding of TFIID to the downstream promoter positions the upstream DNA and facilitates scanning of TBP for a TATA-box and the subsequent engagement of the promoter. Our findings provide a mechanistic model for the specific loading of TBP by TFIID onto the promoter. Structure of human TFIID and mechanism of TBP loading onto promoter DNA.,Patel AB, Louder RK, Greber BJ, Grunberg S, Luo J, Fang J, Liu Y, Ranish J, Hahn S, Nogales E Science. 2018 Nov 15. pii: science.aau8872. doi: 10.1126/science.aau8872. PMID:30442764[15] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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