PDBsum entry 2m5b

Apoptosis

PDB id: 2m5b

Contents

Protein chains

169 a.a.

23 a.a.

PDB id:

2m5b

Name:

Apoptosis

Title:

The nmr structure of the bid-bak complex

Structure:

Bcl-2 homologous antagonist/killer. Chain: a. Synonym: apoptosis regulator bak, bcl-2-like protein 7, bcl2-l-7. Engineered: yes. Human_bid_bh3_sahb. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: bak, bak1, bcl2l7, cdn1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic construct. Organism_taxid: 32630

NMR struc:

20 models

Authors:

T.Moldoveanu,C.R.Grace,R.W.Kriwacki,D.R.Green

Key ref:

T.Moldoveanu et al. (2013). BID-induced structural changes in BAK promote apoptosis. Nat Struct Biol, 20, 589-597. PubMed id: 23604079 DOI: 10.1038/nsmb.2563

Date:

19-Feb-13 Release date: 17-Apr-13

Protein chain

Q16611  (BAK_HUMAN) -  Bcl-2 homologous antagonist/killer from Homo sapiens

Seq: 211 a.a.

Struc: 169 a.a.

Protein chain

P55957  (BID_HUMAN) -  BH3-interacting domain death agonist from Homo sapiens

Seq: 195 a.a.

Struc: 23 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1038/nsmb.2563

Nat Struct Biol 20:589-597 (2013)

PubMed id: 23604079

BID-induced structural changes in BAK promote apoptosis.

T.Moldoveanu, C.R.Grace, F.Llambi, A.Nourse, P.Fitzgerald, K.Gehring, R.W.Kriwacki, D.R.Green.

ABSTRACT

The BCL-2-family protein BAK is responsible for mitochondrial outer-membrane permeabilization (MOMP), which leads to apoptosis. The BCL-2 homology 3 (BH3)-only protein BID activates BAK to perform this function. We report the NMR solution structure of the human BID BH3-BAK complex, which identified the activation site at the canonical BH3-binding groove of BAK. Mutating the BAK BH1 in the groove prevented activation and MOMP but not the binding of BID. BAK BH3 mutations allowed BID binding and activation but blunted function by blocking BAK oligomerization. BAK activation follows a 'hit-and-run' mechanism whereby BID dissociates from the trigger site, which allows BAK oligomerization at an overlapping interface. In contrast, the BH3-only proteins NOXA and BAD are predicted to clash with the trigger site and are not activators of BAK. These findings provide insights into the early stages of BAK activation.