Summary for 8QR1
| Entry DOI | 10.2210/pdb8qr1/pdb |
| EMDB information | 18611 |
| Descriptor | E1A-binding protein p400, Enhancer of polycomb homolog 1, DNA methyltransferase 1-associated protein 1, ... (8 entities in total) |
| Functional Keywords | eukaryotic transcription, histone acetyltransferase, chromatin remodeling, complex, transcription |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 13 |
| Total formula weight | 966838.81 |
| Authors | Li, C.,Smirnova, E.,Schnitzler, C.,Crucifix, C.,Concordet, J.P.,Brion, A.,Poterszman, A.,Schultz, P.,Papai, G.,Ben-Shem, A. (deposition date: 2023-10-06, release date: 2024-08-07, Last modification date: 2024-12-04) |
| Primary citation | Li, C.,Smirnova, E.,Schnitzler, C.,Crucifix, C.,Concordet, J.P.,Brion, A.,Poterszman, A.,Schultz, P.,Papai, G.,Ben-Shem, A. Structure of the human TIP60-C histone exchange and acetyltransferase complex. Nature, 635:764-769, 2024 Cited by PubMed Abstract: Chromatin structure is a key regulator of DNA transcription, replication, and repair. In humans, the TIP60/EP400 complex (TIP60-C) is a 20-subunit assembly that impacts chromatin structure via two enzymatic activities: ATP-dependent exchange of histone H2A/H2B for H2A.Z/H2B and histone acetylation, which in yeast are carried out by two independent complexes, SWR1 and NuA4, respectively. How these activities are merged in humans into one super-complex and what this association entails for their structure, mechanism and recruitment to chromatin is unknown. Here we describe the 2.4-3.3 Å resolution structure of the endogenous human TIP60-C. We find a three lobed architecture composed of SWR1-like (SWR1L) and NuA4-like (NuA4L) parts, that associate with a TRRAP activator-binding module. The huge EP400 subunit harbors the ATPase motor, traverses twice the junction between SWR1L and NuA4L, and constitutes the scaffold of the three-lobed architecture. NuA4L is completely re-arranged compared to its yeast counterpart. TRRAP is flexibly tethered to NuA4L, in stark contrast to its robust connection to the complete opposite side of yeast NuA4. A modeled nucleosome bound to SWR1L, supported by activity tests, suggests that some aspects of the histone exchange mechanism diverge from the yeast example. Furthermore, a fixed actin module, as opposed to the mobile actin subcomplex in SWR1, the flexibility of TRRAP and the weak effect of extra-nucleosomal DNA on exchange activity, lead to a different, activator-based, mode of enlisting TIP60-C to chromatin. PubMed: 39260417DOI: 10.1038/s41586-024-08011-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.4 Å) |
Structure validation
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