2n3a
From Proteopedia
Solution structure of LEDGF/p75 IBD in complex with POGZ peptide (1389-1404)
Structural highlights
Disease[PSIP1_HUMAN] Note=A chromosomal aberration involving PSIP1 is associated with pediatric acute myeloid leukemia (AML) with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes. Translocation t(9;11)(p22;p15) with NUP98. The chimeric transcript is an in-frame fusion of NUP98 exon 8 to PSIP1/LEDGF exon 4. Function[POGZ_HUMAN] Plays a role in mitotic cell cycle progression and is involved in kinetochore assembly and mitotic sister chromatid cohesion. Probably through its association with CBX5 plays a role in mitotic chromosome segregation by regulating aurora kinase B/AURKB activation and AURKB and CBX5 dissociation from chromosome arms.[1] [PSIP1_HUMAN] Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration.[2] Publication Abstract from PubMedLens epithelium-derived growth factor (LEDGF/p75) is an epigenetic reader and attractive therapeutic target involved in HIV integration and the development of mixed lineage leukaemia (MLL1) fusion-driven leukaemia. Besides HIV integrase and the MLL1-menin complex, LEDGF/p75 interacts with various cellular proteins via its integrase binding domain (IBD). Here we present structural characterization of IBD interactions with transcriptional repressor JPO2 and domesticated transposase PogZ, and show that the PogZ interaction is nearly identical to the interaction of LEDGF/p75 with MLL1. The interaction with the IBD is maintained by an intrinsically disordered IBD-binding motif (IBM) common to all known cellular partners of LEDGF/p75. In addition, based on IBM conservation, we identify and validate IWS1 as a novel LEDGF/p75 interaction partner. Our results also reveal how HIV integrase efficiently displaces cellular binding partners from LEDGF/p75. Finally, the similar binding modes of LEDGF/p75 interaction partners represent a new challenge for the development of selective interaction inhibitors. Multiple cellular proteins interact with LEDGF/p75 through a conserved unstructured consensus motif.,Tesina P, Cermakova K, Horejsi M, Prochazkova K, Fabry M, Sharma S, Christ F, Demeulemeester J, Debyser Z, Rijck JD, Veverka V, Rezacova P Nat Commun. 2015 Aug 6;6:7968. doi: 10.1038/ncomms8968. PMID:26245978[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Cermakova, K | Christ, F | Debyser, Z | Demeulemeester, J | Fabry, M | Horejsi, M | Prochazkova, K | Rezacova, P | Rijck, J De | Sharma, S | Tesina, P | Veverka, V | H3k36me3 | Ledgf/p75 | Pogz | Protein binding
