PDBsum entry 2me8

Apoptosis

PDB id: 2me8

Contents

Protein chain

212 a.a.

PDB id:

2me8

Name:

Apoptosis

Title:

Solution structure of bcl-xl in its p53-bound conformation determined with selective isotope labelling of i,l,v sidechains

Structure:

Bcl-2-like protein 1. Chain: a. Fragment: unp residues 1-209. Synonym: bcl2-l-1, apoptosis regulator bcl-x. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: bcl2l1, bcl2l, bclx. Expressed in: escherichia coli. Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

A.Viacava Follis,C.R.Grace,R.W.Kriwacki

Key ref:

A.V.Follis et al. (2014). The DNA-binding domain mediates both nuclear and cytosolic functions of p53. Nat Struct Biol, 21, 535-543. PubMed id: 24814347 DOI: 10.1038/nsmb.2829

Date:

25-Sep-13 Release date: 30-Apr-14

Protein chain

Q07817  (B2CL1_HUMAN) -  Bcl-2-like protein 1 from Homo sapiens

Seq: 233 a.a.

Struc: 212 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/nsmb.2829

Nat Struct Biol 21:535-543 (2014)

PubMed id: 24814347

The DNA-binding domain mediates both nuclear and cytosolic functions of p53.

A.V.Follis, F.Llambi, L.Ou, K.Baran, D.R.Green, R.W.Kriwacki.

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.