X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death
THE Bcl-2 family of proteins regulate programmed cell death by an unknown mechanism1. Here we describe the crystal and solution structures of a Bcl-2 family member, Bcl-xL (ref. 2). The structures consist of two central, primarily hydrophobic α-helices, which are surrounded by amphipathic helices. A...
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sg-ntu-dr.10356-954962023-02-28T17:03:38Z X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death Yoon, Ho Sup Sattler, Michael Muchmore, Steven W. Liang, Heng Meadows, Robert P. Harlan, John E. Nettesheim, David G. Chang, Brian S. Thompson, Craig B. Wong, Sui-Lam Ng, Shi-Chung Fesik, Stephen W. School of Biological Sciences DRNTU::Science::Biological sciences THE Bcl-2 family of proteins regulate programmed cell death by an unknown mechanism1. Here we describe the crystal and solution structures of a Bcl-2 family member, Bcl-xL (ref. 2). The structures consist of two central, primarily hydrophobic α-helices, which are surrounded by amphipathic helices. A 60-residue loop connecting helices αl and α2 was found to be flexible and non-essential for anti-apoptotic activity. The three functionally important Bcl-2 homology regions (BH1, BH2 and BH3)3–5 are in close spatial proximity and form an elongated hydrophobic cleft that may represent the binding site for other Bcl-2 family members. The arrangement of the α-helices in Bcl-xL is reminiscent of the membrane translocation domain of bacterial toxins, in particular diphtheria toxin and the colicins6. The structural similarity may provide a clue to the mechanism of action of the Bcl-2 family of proteins. Accepted version 2012-07-09T03:56:24Z 2019-12-06T19:15:57Z 2012-07-09T03:56:24Z 2019-12-06T19:15:57Z 1996 1996 Journal Article Muchmore, S. W., Sattler, M., Liang, H., Meadows, R. P., Harlan, J. E., Yoon, H. S., et al. (1996). X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature, 381, 335-341. https://hdl.handle.net/10356/95496 http://hdl.handle.net/10220/8302 10.1038/381335a0 en Nature © 1996 Nature Publishing Group. This is the author created version of a work that has been peer reviewed and accepted for publication by Nature, Nature Publishing Group. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [DOI: http://dx.doi.org/10.1038/381335a0 ] application/pdf |
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DRNTU::Science::Biological sciences Yoon, Ho Sup Sattler, Michael Muchmore, Steven W. Liang, Heng Meadows, Robert P. Harlan, John E. Nettesheim, David G. Chang, Brian S. Thompson, Craig B. Wong, Sui-Lam Ng, Shi-Chung Fesik, Stephen W. X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death |
| description |
THE Bcl-2 family of proteins regulate programmed cell death by an unknown mechanism1. Here we describe the crystal and solution structures of a Bcl-2 family member, Bcl-xL (ref. 2). The structures consist of two central, primarily hydrophobic α-helices, which are surrounded by amphipathic helices. A 60-residue loop connecting helices αl and α2 was found to be flexible and non-essential for anti-apoptotic activity. The three functionally important Bcl-2 homology regions (BH1, BH2 and BH3)3–5 are in close spatial proximity and form an elongated hydrophobic cleft that may represent the binding site for other Bcl-2 family members. The arrangement of the α-helices in Bcl-xL is reminiscent of the membrane translocation domain of bacterial toxins, in particular diphtheria toxin and the colicins6. The structural similarity may provide a clue to the mechanism of action of the Bcl-2 family of proteins. |
| author2 |
School of Biological Sciences |
| author_facet |
School of Biological Sciences Yoon, Ho Sup Sattler, Michael Muchmore, Steven W. Liang, Heng Meadows, Robert P. Harlan, John E. Nettesheim, David G. Chang, Brian S. Thompson, Craig B. Wong, Sui-Lam Ng, Shi-Chung Fesik, Stephen W. |
| format |
Article |
| author |
Yoon, Ho Sup Sattler, Michael Muchmore, Steven W. Liang, Heng Meadows, Robert P. Harlan, John E. Nettesheim, David G. Chang, Brian S. Thompson, Craig B. Wong, Sui-Lam Ng, Shi-Chung Fesik, Stephen W. |
| author_sort |
Yoon, Ho Sup |
| title |
X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death |
| title_short |
X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death |
| title_full |
X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death |
| title_fullStr |
X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death |
| title_full_unstemmed |
X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death |
| title_sort |
x-ray and nmr structure of human bcl-xl, an inhibitor of programmed cell death |
| publishDate |
2012 |
| url |
https://hdl.handle.net/10356/95496 http://hdl.handle.net/10220/8302 |
| _version_ |
1759853358709997568 |