PDBsum entry 1mk3

Apoptosis

PDB id: 1mk3

Contents

Protein chain

178 a.a. *

* Residue conservation analysis

PDB id:

1mk3

Name:

Apoptosis

Title:

Solution structure of human bcl-w protein

Structure:

Apoptosis regulator bcl-w. Chain: a. Synonym: bcl-w. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

NMR struc:

10 models

Authors:

A.Y.Denisov,M.S.Madiraju,G.Chen,A.Khadir,P.Beauparlant,G.Attardo, G.C.Shore,K.Gehring

Key ref:

A.Y.Denisov et al. (2003). Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix. J Biol Chem, 278, 21124-21128. PubMed id: 12651847 DOI: 10.1074/jbc.M301798200

Date:

28-Aug-02 Release date: 03-Jun-03

Protein chain

Q92843  (B2CL2_HUMAN) -  Bcl-2-like protein 2 from Homo sapiens

Seq: 193 a.a.

Struc: 178 a.a.*

* PDB and UniProt seqs differ at 10 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M301798200

J Biol Chem 278:21124-21128 (2003)

PubMed id: 12651847

Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix.

A.Y.Denisov, M.S.Madiraju, G.Chen, A.Khadir, P.Beauparlant, G.Attardo, G.C.Shore, K.Gehring.

ABSTRACT

The structure of human BCL-w, an anti-apoptotic member of the BCL-2 family, was determined by triple-resonance NMR spectroscopy and molecular modeling. Introduction of a single amino acid substitution (P117V) significantly improved the quality of the NMR spectra obtained. The cytosolic domain of BCL-w consists of 8 alpha-helices, which adopt a fold similar to that of BCL-xL, BCL-2, and BAX proteins. Pairwise root meant square deviation values were less than 3 A for backbone atoms of structurally equivalent regions. Interestingly, the C-terminal helix alpha8 of BCL-w folds into the BH3-binding hydrophobic cleft of the protein, in a fashion similar to the C-terminal transmembrane helix of BAX. A peptide corresponding to the BH3 region of the pro-apoptotic protein, BID, could displace helix alpha8 from the BCL-w cleft, resulting in helix unfolding. Deletion of helix alpha8 increased binding affinities of BCL-w for BAK and BID BH3-peptides, indicating that this helix competes for peptide binding to the hydrophobic cleft. These results suggest that although the cytosolic domain of BCL-w exhibits an overall structure similar to that of BCL-xL and BCL-2, the unique organization of its C-terminal helix may modulate BCL-w interactions with pro-apoptotic binding partners.

Selected figure(s)

Figure 4.
FIG. 4. Stereoview of the backbone of 10 low energy BCL-w structures. The structures were superposed based on all -helical residues only.

Figure 5.
FIG. 5. The ribbon representations of the structures of BCL-w (P117V) (a), BAX (b), and BCL-x[L]/BAK-BH3-peptide complex (c). Odd numbered helices are blue, and even numbered helices are green. The C-terminal -helices in BCL-w and BAX proteins and the bound peptide in the BCL-x[L] complex are red. d presents a view of the BCL-w binding cleft and bound C-terminal helix. Helix 8 and its hydrophobic residues are shown in green. The cleft surface is blue, red, and yellow to show positive (Arg, Lys, His), negative (Asp, Glu), and hydrophobic (Val, Leu, Ile, Ala, Phe, Tyr, Trp) residues, respectively. Other residue types are gray.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 21124-21128) copyright 2003.

Figures were selected by the author.