6nfx
From Proteopedia
MBTD1 MBT repeats
Structural highlights
FunctionEPC1_HUMAN Component of the NuA4 histone acetyltransferase (HAT) complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:14966270). The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) by promoting homologous recombination (HR) (PubMed:27153538). The NuA4 complex is also required for spermatid development by promoting acetylation of histones: histone acetylation is required for histone replacement during the transition from round to elongating spermatids (By similarity). In the NuA4 complex, EPC1 is required to recruit MBTD1 into the complex (PubMed:32209463).[UniProtKB:Q8C9X6][1] [2] [3] MBTD1_HUMAN Putative Polycomb group (PcG) protein. PcG proteins maintain the transcriptionally repressive state of genes, probably via a modification of chromatin, rendering it heritably changed in its expressibility (By similarity). Specifically binds to monomethylated and dimethylated 'Lys-20' on histone H4. Publication Abstract from PubMedMBTD1, a H4K20me reader, has recently been identified as a component of the NuA4/TIP60 acetyltransferase complex, regulating gene expression and DNA repair. NuA4/TIP60 inhibits 53BP1 binding to chromatin through recognition of the H4K20me mark by MBTD1 and acetylation of H2AK15, blocking the ubiquitination mark required for 53BP1 localization at DNA breaks. The NuA4/TIP60 non-catalytic subunit EPC1 enlists MBTD1 into the complex, but the detailed molecular mechanism remains incompletely explored. Here, we present the crystal structure of the MBTD1-EPC1 complex, revealing a hydrophobic C-terminal fragment of EPC1 engaging the MBT repeats of MBTD1 in a site distinct from the H4K20me binding site. Different cellular assays validate the physiological significance of the key residues involved in the MBTD1-EPC1 interaction. Our study provides a structural framework for understanding the mechanism by which MBTD1 recruits the NuA4/TIP60 acetyltransferase complex to influence transcription and DNA repair pathway choice. Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex.,Zhang H, Devoucoux M, Song X, Li L, Ayaz G, Cheng H, Tempel W, Dong C, Loppnau P, Cote J, Min J Cell Rep. 2020 Mar 24;30(12):3996-4002.e4. doi: 10.1016/j.celrep.2020.03.003. PMID:32209463[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Arrowsmith CH | Bountra C | Edwards AM | Min J | Tempel W | Zhang H
