PDBsum entry 4zih

Apoptosis

PDB id: 4zih

Contents

Protein chains

145 a.a.

16 a.a.

Waters ×14

PDB id:

4zih

Name:

Apoptosis

Title:

Crystal structure of core/latch dimer of bax in complex with bimbh3mini

Structure:

Apoptosis regulator bax. Chain: a. Synonym: bcl-2-like protein 4,bcl2-l-4. Engineered: yes. Mutation: yes. Bcl-2-like protein 11. Chain: b. Fragment: bh3 motif, unp residues 141-160. Synonym: bcl2-l-11,bcl2-interacting mediator of cell death.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: bax, bcl2l4. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Resolution:

2.50Å R-factor: 0.189 R-free: 0.233

Authors:

A.Y.Robin,K.Krishna Kumar,D.Westphal,A.Z.Wardak,G.V.Thompson, G.Dewson,P.M.Colman,P.E.Czabotar

Key ref:

A.Y.Robin et al. (2015). Crystal structure of Bax bound to the BH3 peptide of Bim identifies important contacts for interaction. Cell Death Dis, 6, e1809. PubMed id: 26158515 DOI: 10.1038/cddis.2015.141

Date:

28-Apr-15 Release date: 22-Jul-15

Protein chain

Q07812  (BAX_HUMAN) -  Apoptosis regulator BAX from Homo sapiens

Seq: 192 a.a.

Struc: 145 a.a.*

Protein chain

O43521  (B2L11_HUMAN) -  Bcl-2-like protein 11 from Homo sapiens

Seq: 198 a.a.

Struc: 16 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1038/cddis.2015.141

Cell Death Dis 6:e1809 (2015)

PubMed id: 26158515

Crystal structure of Bax bound to the BH3 peptide of Bim identifies important contacts for interaction.

A.Y.Robin, K.Krishna Kumar, D.Westphal, A.Z.Wardak, G.V.Thompson, G.Dewson, P.M.Colman, P.E.Czabotar.

ABSTRACT

The BH3-only protein Bim is a potent direct activator of the proapoptotic effector protein Bax, but the structural basis for its activity has remained poorly defined. Here we describe the crystal structure of the BimBH3 peptide bound to BaxΔC26 and structure-based mutagenesis studies. Similar to BidBH3, the BimBH3 peptide binds into the cognate surface groove of Bax using the conserved hydrophobic BH3 residues h1-h4. However, the structure and mutagenesis data show that Bim is less reliant compared with Bid on its 'h0' residues for activating Bax and that a single amino-acid difference between Bim and Bid encodes a fivefold difference in Bax-binding potency. Similar to the structures of BidBH3 and BaxBH3 bound to BaxΔC21, the structure of the BimBH3 complex with BaxΔC displays a cavity surrounded by Bax α1, α2, α5 and α8. Our results are consistent with a model in which binding of an activator BH3 domain to the Bax groove initiates separation of its core (α2-α5) and latch (α6-α8) domains, enabling its subsequent dimerisation and the permeabilisation of the mitochondrial outer membrane.