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PDBsum entry 1mk3
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Solution structure of human bcl-W: modulation of ligand binding by the c-Terminal helix.
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Authors
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A.Y.Denisov,
M.S.Madiraju,
G.Chen,
A.Khadir,
P.Beauparlant,
G.Attardo,
G.C.Shore,
K.Gehring.
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Ref.
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J Biol Chem, 2003,
278,
21124-21128.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2003,
278,
21124-21128)
copyright 2003.
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