4CZZ

Histone demethylase LSD1(KDM1A)-CoREST3 Complex

4CZZ の概要

• エントリーDOI: 10.2210/pdb4czz/pdb
• 分子名称: LYSINE-SPECIFIC HISTONE DEMETHYLASE 1A, REST COREPRESSOR 3, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: oxidoreductase, corest, rcor2, rcor3, lsd1, hdac1/2
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Nucleus : O60341 Q9P2K3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 156926.09

構造登録者

Barrios, A.P.,Gomez, A.V.,Saez, J.E.,Ciossani, G.,Toffolo, E.,Battaglioli, E.,Mattevi, A.,Andres, M.E. (登録日: 2014-04-23, 公開日: 2014-06-11, 最終更新日: 2023-12-20)

主引用文献

Barrios, A.P.,Gomez, A.V.,Saez, J.E.,Ciossani, G.,Toffolo, E.,Battaglioli, E.,Mattevi, A.,Andres, M.E.
Differential Properties of Transcriptional Complexes Formed by the Corest Family.
Mol.Cell.Biol., 34:2760-, 2014

PubMed Abstract: Mammalian genomes harbor three CoREST genes. rcor1 encodes CoREST (CoREST1), and the paralogues rcor2 and rcor3 encode CoREST2 and CoREST3, respectively. Here, we describe specific properties of transcriptional complexes formed by CoREST proteins with the histone demethylase LSD1/KDM1A and histone deacetylases 1 and 2 (HDAC1/2) and the finding that all three CoRESTs are expressed in the adult rat brain. CoRESTs interact equally strongly with LSD1/KDM1A. Structural analysis shows that the overall conformation of CoREST3 is similar to that of CoREST1 complexed with LSD1/KDM1A. Nonetheless, transcriptional repressive capacity of CoREST3 is lower than that of CoREST1, which correlates with the observation that CoREST3 leads to a reduced LSD1/KDM1A catalytic efficiency. Also, CoREST2 shows a lower transcriptional repression than CoREST1, which is resistant to HDAC inhibitors. CoREST2 displays lower interaction with HDAC1/2, which is barely present in LSD1/KDM1A-CoREST2 complexes. A nonconserved leucine in the first SANT domain of CoREST2 severely weakens its association with HDAC1/2. Furthermore, CoREST2 mutants with increased HDAC1/2 interaction and those without HDAC1/2 interaction exhibit equivalent transcriptional repression capacities, indicating that CoREST2 represses in an HDAC-independent manner. In conclusion, differences among CoREST proteins are instrumental in the modulation of protein-protein interactions and catalytic activities of LSD1/KDM1A-CoREST-HDAC complexes, fine-tuning gene expression regulation.

PubMed: 24820421
DOI: 10.1128/MCB.00083-14

実験手法

X-RAY DIFFRACTION (3 Å)