2N3A
Solution structure of LEDGF/p75 IBD in complex with POGZ peptide (1389-1404)
Summary for 2N3A
| Entry DOI | 10.2210/pdb2n3a/pdb |
| NMR Information | BMRB: 25639 |
| Descriptor | Pogo transposable element with ZNF domain, PC4 and SFRS1-interacting protein (2 entities in total) |
| Functional Keywords | ledgf/p75, pogz, h3k36me3, protein binding |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus: Q7Z3K3 O75475 |
| Total number of polymer chains | 2 |
| Total formula weight | 11180.80 |
| Authors | Tesina, P.,Cermakova, K.,Horejsi, M.,Prochazkova, K.,Fabry, M.,Sharma, S.,Christ, F.,Demeulemeester, J.,Debyser, Z.,De Rijck, J.,Veverka, V.,Rezacova, P. (deposition date: 2015-05-26, release date: 2015-08-19, Last modification date: 2024-05-01) |
| Primary citation | Tesina, P.,Cermakova, K.,Horejsi, M.,Prochazkova, K.,Fabry, M.,Sharma, S.,Christ, F.,Demeulemeester, J.,Debyser, Z.,Rijck, J.D.,Veverka, V.,Rezacova, P. Multiple cellular proteins interact with LEDGF/p75 through a conserved unstructured consensus motif. Nat Commun, 6:7968-7968, 2015 Cited by PubMed Abstract: Lens 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. PubMed: 26245978DOI: 10.1038/ncomms8968 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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