1MK3

SOLUTION STRUCTURE OF HUMAN BCL-W PROTEIN

1MK3 の概要

• エントリーDOI: 10.2210/pdb1mk3/pdb
• 分子名称: Apoptosis regulator Bcl-W (1 entity in total)
• 機能のキーワード: bcl-w protein, apoptotis, apoptosis
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion membrane; Peripheral membrane protein: Q92843
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19659.88

構造登録者

Denisov, A.Y.,Madiraju, M.S.,Chen, G.,Khadir, A.,Beauparlant, P.,Attardo, G.,Shore, G.C.,Gehring, K. (登録日: 2002-08-28, 公開日: 2003-06-03, 最終更新日: 2024-05-22)

主引用文献

Denisov, A.Y.,Madiraju, M.S.,Chen, G.,Khadir, A.,Beauparlant, P.,Attardo, G.,Shore, G.C.,Gehring, K.
Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix
J.BIOL.CHEM., 278:21124-21128, 2003

PubMed 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.

PubMed: 12651847
DOI: 10.1074/jbc.M301798200

実験手法

SOLUTION NMR