5HT6

Crystal structure of the SET domain of the human MLL5 methyltransferase

5HT6 の概要

• エントリーDOI: 10.2210/pdb5ht6/pdb
• 分子名称: Histone-lysine N-methyltransferase 2E (2 entities in total)
• 機能のキーワード: set domain, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus speckle . Isoform NKp44L: Cytoplasm : Q8IZD2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32214.98

構造登録者

le Maire, A.,Mas-y-Mas, S.,Dumas, C.,Lebedev, A. (登録日: 2016-01-26, 公開日: 2016-11-16, 最終更新日: 2024-05-08)

主引用文献

Mas-Y-Mas, S.,Barbon, M.,Teyssier, C.,Demene, H.,Carvalho, J.E.,Bird, L.E.,Lebedev, A.,Fattori, J.,Schubert, M.,Dumas, C.,Bourguet, W.,le Maire, A.
The Human Mixed Lineage Leukemia 5 (MLL5), a Sequentially and Structurally Divergent SET Domain-Containing Protein with No Intrinsic Catalytic Activity.
Plos One, 11:e0165139-e0165139, 2016

PubMed Abstract: Mixed Lineage Leukemia 5 (MLL5) plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. Chromatin binding is ensured by its plant homeodomain (PHD) through a direct interaction with the N-terminus of histone H3 (H3). In addition, MLL5 contains a Su(var)3-9, Enhancer of zeste, Trithorax (SET) domain, a protein module that usually displays histone lysine methyltransferase activity. We report here the crystal structure of the unliganded SET domain of human MLL5 at 2.1 Å resolution. Although it shows most of the canonical features of other SET domains, both the lack of key residues and the presence in the SET-I subdomain of an unusually large loop preclude the interaction of MLL5 SET with its cofactor and substrate. Accordingly, we show that MLL5 is devoid of any in vitro methyltransferase activity on full-length histones and histone H3 peptides. Hence, the three dimensional structure of MLL5 SET domain unveils the structural basis for its lack of methyltransferase activity and suggests a new regulatory mechanism.

PubMed: 27812132
DOI: 10.1371/journal.pone.0165139

実験手法

X-RAY DIFFRACTION (2.093 Å)