2LM0

Solution structure of the AF4-AF9 complex

Summary for 2LM0

• Entry DOI: 10.2210/pdb2lm0/pdb
• NMR Information: BMRB: 18094
• Descriptor: AF4/FMR2 family member 1/Protein AF-9 chimera (1 entity in total)
• Functional Keywords: intrinsically disordered, nuclear protein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (By similarity): P42568
• Total number of polymer chains: 1
• Total formula weight: 14340.59

Authors

Leach, B.I.,Kuntimaddi, A.,Schmidt, C.R.,Cierpicki, T.,Johnson, S.A.,Bushweller, J.H. (deposition date: 2011-11-18, release date: 2013-01-09, Last modification date: 2024-05-01)

Primary citation

Leach, B.I.,Kuntimaddi, A.,Schmidt, C.R.,Cierpicki, T.,Johnson, S.A.,Bushweller, J.H.
Leukemia Fusion Target AF9 Is an Intrinsically Disordered Transcriptional Regulator that Recruits Multiple Partners via Coupled Folding and Binding.
Structure, 21:176-183, 2013

PubMed Abstract: Mixed lineage leukemia (MLL) fusion proteins cause oncogenic transformation of hematopoietic cells by constitutive recruitment of elongation factors to HOX promoters, resulting in overexpression of target genes. The structural basis of transactivation by MLL fusion partners remains undetermined. We show that the ANC1 homology domain (AHD) of AF9, one of the most common MLL translocation partners, is intrinsically disordered and recruits multiple transcription factors through coupled folding and binding. We determined the structure of the AF9 AHD in complex with the elongation factor AF4 and show that aliphatic residues, which are conserved in each of the AF9 binding partners, form an integral part of the hydrophobic core of the complex. Nuclear magnetic resonance relaxation measurements show that AF9 retains significant dynamic behavior which may facilitate exchange between disordered partners. We propose that AF9 functions as a signaling hub that regulates transcription through dynamic recruitment of cofactors in normal hematopoiesis and in acute leukemia.

PubMed: 23260655
DOI: 10.1016/j.str.2012.11.011

Experimental method

SOLUTION NMR