Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/94051
Title: Solution structure of the antiapoptotic protein bcl-2
Authors: Petros, Andrew M.
Nettesheim, David G.
Kim, Daniel H.
Matayoshi, Edmund D.
Fesik, Stephen W.
Medek, Ales
Yoon, Ho Sup
Swift, Kerry
Oltersdorf, Tilman
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2001
Source: Petros, A. M., Medek, A., Nettesheim, D. G., Kim, D. H., Yoon, H. S., Swift, K., et al. (2001). Solution structure of the antiapoptotic protein bcl-2. Proceedings of the National Academy of Sciences, 98(6), 3012-3017.
Abstract: The structures of two isoforms of Bcl-2 that differ by two amino acids have been determined by NMR spectroscopy. Because wild-type Bcl-2 behaved poorly in solution, the structures were determined by using Bcl-2/Bcl-xL chimeras in which part of the putative unstructured loop of Bcl-2 was replaced with a shortened loop from Bcl-xL. These chimeric proteins have a low pI compared with the wild-type protein and are soluble. The structures of the two Bcl-2 isoforms consist of 6 α-helices with a hydrophobic groove on the surface similar to that observed for the homologous protein, Bcl-xL. Comparison of the Bcl-2 structures to that of Bcl-xL shows that although the overall fold is the same, there are differences in the structural topology and electrostatic potential of the binding groove. Although the structures of the two isoforms of Bcl-2 are virtually identical, differences were observed in the ability of the proteins to bind to a 25-residue peptide from the proapoptotic Bad protein and a 16-residue peptide from the proapoptotic Bak protein. These results suggest that there are subtle differences in the hydrophobic binding groove in Bcl-2 that may translate into differences in antiapoptotic activity for the two isoforms.
URI: https://hdl.handle.net/10356/94051
http://hdl.handle.net/10220/7509
DOI: 10.1073/pnas.041619798
Rights: © 2001 National Academy of Sciences. This is the author created version of a work that has been peer reviewed and accepted for publication by Proceedings of the National Academy of Sciences, National Academy of Sciences.  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: http://dx.doi.org/10.1073/pnas.041619798
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Conference Papers

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