7EDP

Crystal structure of AF10-DOT1L complex

Summary for 7EDP

• Entry DOI: 10.2210/pdb7edp/pdb
• Descriptor: Histone-lysine N-methyltransferase, H3 lysine-79 specific, Protein AF-10 (3 entities in total)
• Functional Keywords: complex, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 9723.36

Authors

Chen, S.,Zhou, Z. (deposition date: 2021-03-16, release date: 2021-04-28, Last modification date: 2023-11-29)

Primary citation

Zhou, Z.,Kang, S.,Huang, Z.,Zhou, Z.,Chen, S.
Structural characteristics of coiled-coil regions in AF10-DOT1L and AF10-inhibitory peptide complex.
J Leukoc Biol, 110:1091-1099, 2021

PubMed Abstract: The interaction of the solo H3K79 methyltransferase DOT1-like (DOT1L) and its regulatory factor ALL1-fused gene from chromosome 10 protein (AF10) is crucial for the transcription of developmental genes such as HOXA in acute leukemia. The octapeptide motif and leucine zipper region of AF10 is responsible for binding DOT1L and catalyzing H3K79 monomethylation to demethylation. However, the characteristics of the mechanism between DOT1L and AF10 are not clear. Here, we present the crystal structures of coiled-coil regions of DOT1L-AF10 and AF10-inhibitory peptide, demonstrating the inhibitory peptide could form a compact complex with AF10 via a different recognition pattern. Furthermore, an inhibitory peptide with structure-based optimization is identified and decreases the HOXA gene expression in a human cell line. Our studies provide an innovative pharmacologic basis for therapeutic intervention in leukemia.

PubMed: 33993518
DOI: 10.1002/JLB.1MA0421-010R

Experimental method

X-RAY DIFFRACTION (2.2 Å)