2LXT
Allosteric communication in the KIX domain proceeds through dynamic re-packing of the hydrophobic core
Summary for 2LXT
| Entry DOI | 10.2210/pdb2lxt/pdb |
| Related | 2LXS |
| NMR Information | BMRB: 18695 |
| Descriptor | CREB-binding protein, Histone-lysine N-methyltransferase MLL, Cyclic AMP-responsive element-binding protein 1 (3 entities in total) |
| Functional Keywords | creb binding protein, mixed-lineage leukemia activation domain, phosphorylated kinase inducible domain, creb, ternary complex, transferase-protein binding complex, transferase/protein binding |
| Biological source | Homo sapiens (human) More |
| Cellular location | Cytoplasm: Q92793 Nucleus. MLL cleavage product N320: Nucleus. MLL cleavage product C180: Nucleus: Q03164 Nucleus: P16220 |
| Total number of polymer chains | 3 |
| Total formula weight | 16359.48 |
| Authors | Bruschweiler, S.,Schanda, P.,Konrat, R.,Tollinger, M. (deposition date: 2012-08-31, release date: 2013-06-12, Last modification date: 2024-11-20) |
| Primary citation | Bruschweiler, S.,Konrat, R.,Tollinger, M. Allosteric communication in the KIX domain proceeds through dynamic repacking of the hydrophobic core. Acs Chem.Biol., 8:1600-1610, 2013 Cited by PubMed Abstract: The KIX domain of the transcriptional coactivator CREB binding protein (CBP) co-operatively mediates interactions between transcription factors. Binding of the transcription factor mixed-lineage leukemia (MLL) induces the formation of a low-populated conformer of KIX that resembles the conformation of the KIX domain in the presence of a second transcription factor molecule. NMR spin relaxation studies have previously shown that allosteric coupling proceeds through a network of hydrophobic core residues that bridge the two binding sites. Here we describe high-resolution NMR solution structures of the binary complex of KIX with MLL and the ternary complex of KIX formed with MLL and phosphorylated kinase inducible domain of CREB (pKID) as a second ligand. We show that binding of pKID to the binary complex of KIX with MLL is accompanied by a defined repacking of the allosteric network in the hydrophobic core of the protein. Rotamer populations derived from methyl group (13)C chemical shifts reveal a dynamic contribution to the repacking process that is not captured by the structural coordinates and exemplify the dynamic nature of allosteric communication in the KIX domain. PubMed: 23651431DOI: 10.1021/cb4002188 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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