6CKO

Crystal structure of an AF10 fragment

6CKO の概要

• エントリーDOI: 10.2210/pdb6cko/pdb
• 分子名称: Protein AF-10, Histone-lysine N-methyltransferase, H3 lysine-79 specific, ZINC ION, ... (5 entities in total)
• 機能のキーワード: structural genomics, structural genomics consortium, sgc, dna binding protein-transferase complex, dna binding protein/transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : P55197 F1Q4W7
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 29854.48

構造登録者

Zhang, H.,Tempel, W.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Min, J.,Structural Genomics Consortium (SGC) (登録日: 2018-02-28, 公開日: 2018-03-21, 最終更新日: 2024-10-30)

主引用文献

Zhang, H.,Zhou, B.,Qin, S.,Xu, J.,Harding, R.,Tempel, W.,Nayak, V.,Li, Y.,Loppnau, P.,Dou, Y.,Min, J.
Structural and functional analysis of the DOT1L-AF10 complex reveals mechanistic insights into MLL-AF10-associated leukemogenesis.
Genes Dev., 32:341-346, 2018

PubMed Abstract: The mixed-lineage leukemia (MLL)-AF10 fusion oncoprotein recruits DOT1L to the homeobox A () gene cluster through its octapeptide motif leucine zipper (OM-LZ), thereby inducing and maintaining the MLL-AF10-associated leukemogenesis. However, the recognition mechanism between DOT1L and MLL-AF10 is unclear. Here, we present the crystal structures of both apo AF10 and its complex with the coiled-coil domain of DOT1L. Disruption of the DOT1L-AF10 interface abrogates MLL-AF10-associated leukemic transformation. We further show that zinc stabilizes the DOT1L-AF10 complex and may be involved in the regulation of the gene expression. Our studies may also pave the way for the rational design of therapeutic drugs against -rearranged leukemia.

PubMed: 29563185
DOI: 10.1101/gad.311639.118

実験手法

X-RAY DIFFRACTION (2 Å)