6CKN

Crystal structure of an AF10 fragment

Summary for 6CKN

• Entry DOI: 10.2210/pdb6ckn/pdb
• Descriptor: Protein AF-10, UNKNOWN ATOM OR ION (2 entities in total)
• Functional Keywords: structural genomics, structural genomics consortium, sgc, dna binding protein
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : P55197
• Total number of polymer chains: 2
• Total formula weight: 17583.63

Authors

Qin, S.,Tempel, W.,Li, Y.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Min, J.,Structural Genomics Consortium (SGC) (deposition date: 2018-02-28, release date: 2018-03-21, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.49 Å)