5y81

From Proteopedia

NuA4 TEEAA sub-complex

5y81, resolution 4.70Å

Structural highlights

5y81 is a 8 chain structure with sequence from Saccharomyces cerevisiae and Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.7Å
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TRA1_YEAST Essential component of histone acetyltransferase (HAT) complexes, which serves as a target for activators during recruitment of HAT complexes. Essential for vegetative growth. Functions as a component of the transcription regulatory histone acetylation (HAT) complexes SAGA, SALSA and SLIK. SAGA is involved in RNA polymerase II-dependent transcriptional regulation of approximately 10% of yeast genes. At the promoters, SAGA is required for recruitment of the basal transcription machinery. It influences RNA polymerase II transcriptional activity through different activities such as TBP interaction (SPT3, SPT8 and SPT20) and promoter selectivity, interaction with transcription activators (GCN5, ADA2, ADA3 and TRA1), and chromatin modification through histone acetylation (GCN5) and deubiquitination (UBP8). SAGA acetylates nucleosomal histone H3 to some extent (to form H3K9ac, H3K14ac, H3K18ac and H3K23ac). SAGA interacts with DNA via upstream activating sequences (UASs). SALSA, an altered form of SAGA, may be involved in positive transcriptional regulation. SLIK is proposed to have partly overlapping functions with SAGA. It preferentially acetylates methylated histone H3, at least after activation at the GAL1-10 locus.^[1] ^[2]

Publication Abstract from PubMed

The NuA4/TIP60 acetyltransferase complex is required for gene regulation, DNA repair and cell cycle progression. The limited structural information impeded understanding of NuA4/TIP60 assembly and regulatory mechanism. Here, we report the 4.7 A cryo-electron microscopy (cryo-EM) structure of a NuA4/TIP60 TEEAA assembly (Tra1, Eaf1, Eaf5, actin and Arp4) and the 7.6 A cryo-EM structure of a TEEAA-piccolo assembly (Esa1, Epl1, Yng2 and Eaf6). The Tra1 and Eaf1 constitute the assembly scaffold. The Eaf1 SANT domain tightly binds to the LBE and FATC domains of Tra1 by ionic interactions. The actin/Arp4 peripherally associates with Eaf1 HSA domain. The Eaf5/7/3 (TINTIN) and piccolo modules largely pack against the FAT and HEAT repeats of Tra1 and their association depends on Eaf1 N-terminal and HSA regions, respectively. These structures elucidate the detailed architecture and molecular interactions between NuA4 subunits and offer exciting insights into the scaffolding and regulatory mechanisms of Tra1 pseudokinase.

Architecture of the Saccharomyces cerevisiae NuA4/TIP60 complex.,Wang X, Ahmad S, Zhang Z, Cote J, Cai G Nat Commun. 2018 Mar 20;9(1):1147. doi: 10.1038/s41467-018-03504-5. PMID:29559617^[3]

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

References

↑ Grant PA, Eberharter A, John S, Cook RG, Turner BM, Workman JL. Expanded lysine acetylation specificity of Gcn5 in native complexes. J Biol Chem. 1999 Feb 26;274(9):5895-900. PMID:10026213
↑ Brown CE, Howe L, Sousa K, Alley SC, Carrozza MJ, Tan S, Workman JL. Recruitment of HAT complexes by direct activator interactions with the ATM-related Tra1 subunit. Science. 2001 Jun 22;292(5525):2333-7. PMID:11423663 doi:http://dx.doi.org/10.1126/science.1060214
↑ Wang X, Ahmad S, Zhang Z, Cote J, Cai G. Architecture of the Saccharomyces cerevisiae NuA4/TIP60 complex. Nat Commun. 2018 Mar 20;9(1):1147. doi: 10.1038/s41467-018-03504-5. PMID:29559617 doi:http://dx.doi.org/10.1038/s41467-018-03504-5