7ktr | pdb_00007ktr
Cryo-EM structure of the human SAGA coactivator complex (TRRAP, core)
Structural highlights
DiseaseTRRAP_HUMAN Rare autosomal dominant non-syndromic sensorineural deafness type DFNA. TRRAP mutation Phe-722 has been frequently found in cutaneous malignant melanoma, suggesting that TRRAP may play a role in the pathogenesis of melanoma.[1] The disease is caused by variants affecting the gene represented in this entry. The disease may be caused by variants affecting the gene represented in this entry. FunctionTRRAP_HUMAN Adapter protein, which is found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT), which gives a specific tag for epigenetic transcription activation. Component of the NuA4 histone acetyltransferase complex which is responsible for acetylation of nucleosomal histones H4 and H2A. Plays a central role in MYC transcription activation, and also participates in cell transformation by MYC. Required for p53/TP53-, E2F1- and E2F4-mediated transcription activation. Also involved in transcription activation mediated by the adenovirus E1A, a viral oncoprotein that deregulates transcription of key genes. Probably acts by linking transcription factors such as E1A, MYC or E2F1 to HAT complexes such as STAGA thereby allowing transcription activation. Probably not required in the steps following histone acetylation in processes of transcription activation. May be required for the mitotic checkpoint and normal cell cycle progression. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. May play a role in the formation and maintenance of the auditory system (By similarity).[UniProtKB:A0A0R4ITC5][2] [3] [4] [5] [6] [7] [8] [9] Publication Abstract from PubMedThe SAGA complex is a regulatory hub involved in gene regulation, chromatin modification, DNA damage repair and signaling. While structures of yeast SAGA (ySAGA) have been reported, there are noteworthy functional and compositional differences for this complex in metazoans. Here we present the cryogenic-electron microscopy (cryo-EM) structure of human SAGA (hSAGA) and show how the arrangement of distinct structural elements results in a globally divergent organization from that of yeast, with a different interface tethering the core module to the TRRAP subunit, resulting in a dramatically altered geometry of functional elements and with the integration of a metazoan-specific splicing module. Our hSAGA structure reveals the presence of an inositol hexakisphosphate (InsP(6)) binding site in TRRAP and an unusual property of its pseudo-(Psi)PIKK. Finally, we map human disease mutations, thus providing the needed framework for structure-guided drug design of this important therapeutic target for human developmental diseases and cancer. Structure of the human SAGA coactivator complex.,Herbst DA, Esbin MN, Louder RK, Dugast-Darzacq C, Dailey GM, Fang Q, Darzacq X, Tjian R, Nogales E Nat Struct Mol Biol. 2021 Dec;28(12):989-996. doi: 10.1038/s41594-021-00682-7. , Epub 2021 Nov 22. PMID:34811519[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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