1mk3
From Proteopedia
(New page: 200px<br /> <applet load="1mk3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mk3" /> '''SOLUTION STRUCTURE OF HUMAN BCL-W PROTEIN''...) |
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| - | [[Image:1mk3.gif|left|200px]]<br /> | + | [[Image:1mk3.gif|left|200px]]<br /><applet load="1mk3" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1mk3" size=" | + | |
caption="1mk3" /> | caption="1mk3" /> | ||
'''SOLUTION STRUCTURE OF HUMAN BCL-W PROTEIN'''<br /> | '''SOLUTION STRUCTURE OF HUMAN BCL-W PROTEIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structure of human BCL-w, an anti-apoptotic member of the BCL-2 | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1MK3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1MK3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MK3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Beauparlant, P.]] | [[Category: Beauparlant, P.]] | ||
[[Category: Chen, G.]] | [[Category: Chen, G.]] | ||
| - | [[Category: Denisov, A | + | [[Category: Denisov, A Y.]] |
[[Category: Gehring, K.]] | [[Category: Gehring, K.]] | ||
[[Category: Khadir, A.]] | [[Category: Khadir, A.]] | ||
| - | [[Category: Madiraju, M | + | [[Category: Madiraju, M S.]] |
| - | [[Category: Shore, G | + | [[Category: Shore, G C.]] |
[[Category: apoptotis]] | [[Category: apoptotis]] | ||
[[Category: bcl-w protein]] | [[Category: bcl-w protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:55:59 2008'' |
Revision as of 11:55, 21 February 2008
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SOLUTION STRUCTURE OF HUMAN BCL-W PROTEIN
Overview
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.
About this Structure
1MK3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix., Denisov AY, Madiraju MS, Chen G, Khadir A, Beauparlant P, Attardo G, Shore GC, Gehring K, J Biol Chem. 2003 Jun 6;278(23):21124-8. Epub 2003 Mar 21. PMID:12651847
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