2ME8
Solution Structure of BCL-xL in its p53-bound conformation determined with selective isotope labelling of I,L,V sidechains
Summary for 2ME8
| Entry DOI | 10.2210/pdb2me8/pdb |
| Related | 2ME9 2MEJ |
| NMR Information | BMRB: 19520 |
| Descriptor | Bcl-2-like protein 1 (1 entity in total) |
| Functional Keywords | bcl-xl, p53, apoptosis, bcl-2 family, cytoplasmic p53, selective labeling |
| Biological source | Homo sapiens (human) |
| Cellular location | Isoform Bcl-X(L): Mitochondrion inner membrane (By similarity): Q07817 |
| Total number of polymer chains | 1 |
| Total formula weight | 23669.94 |
| Authors | Viacava Follis, A.,Grace, C.R.,Kriwacki, R.W. (deposition date: 2013-09-25, release date: 2014-04-30, Last modification date: 2024-05-15) |
| Primary citation | Follis, A.V.,Llambi, F.,Ou, L.,Baran, K.,Green, D.R.,Kriwacki, R.W. The DNA-binding domain mediates both nuclear and cytosolic functions of p53. Nat.Struct.Mol.Biol., 21:535-543, 2014 Cited by PubMed Abstract: Under conditions of genotoxic stress, human p53 activates the apoptotic effectors BAX or BAK to result in mitochondrial outer-membrane permeabilization and apoptosis. Antiapoptotic BCL-2 family member BCL-xL opposes this activity by sequestering cytosolic p53 via association with its DNA-binding domain, an interaction enhanced by p53 tetramerization. Here we characterized the BCL-xL-p53 complex by NMR spectroscopy and modulated it through mutagenesis to determine the relative contributions of BCL-xL's interactions with p53 or other BCL-2 family proteins to the BCL-xL-dependent inhibition of UV irradiation-induced apoptosis. Under our experimental conditions, one-third of the antiapoptotic activity of BCL-xL was mediated by p53 sequestration and the remaining two-thirds through sequestration of proapoptotic BCL-2 family members. Our studies define the contributions of cytosolic p53 to UV irradiation-induced apoptosis and provide opportunities to explore its contributions to other p53-dependent apoptotic signaling pathways. PubMed: 24814347DOI: 10.1038/nsmb.2829 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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