Structural highlights
2lm0 is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
|
| Gene: | AFF1, AF4, FEL, MLLT2, PBM1, MLLT3, AF9, YEATS3 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[AFF1_HUMAN] Precursor B-cell acute lymphoblastic leukemia. A chromosomal aberration involving AFF1 is associated with acute leukemias. Translocation t(4;11)(q21;q23) with KMT2A/MLL1. The result is a rogue activator protein.
Publication Abstract from PubMed
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.
Leukemia Fusion Target AF9 Is an Intrinsically Disordered Transcriptional Regulator that Recruits Multiple Partners via Coupled Folding and Binding.,Leach BI, Kuntimaddi A, Schmidt CR, Cierpicki T, Johnson SA, Bushweller JH Structure. 2012 Dec 19. pii: S0969-2126(12)00426-1. doi:, 10.1016/j.str.2012.11.011. PMID:23260655[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Leach BI, Kuntimaddi A, Schmidt CR, Cierpicki T, Johnson SA, Bushweller JH. Leukemia Fusion Target AF9 Is an Intrinsically Disordered Transcriptional Regulator that Recruits Multiple Partners via Coupled Folding and Binding. Structure. 2012 Dec 19. pii: S0969-2126(12)00426-1. doi:, 10.1016/j.str.2012.11.011. PMID:23260655 doi:http://dx.doi.org/10.1016/j.str.2012.11.011
