Solution structure of the antiapoptotic protein bcl-2
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 wit...
| Main Authors: | , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Conference Paper |
| Language: | English |
| Published: |
2012
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/94051 http://hdl.handle.net/10220/7509 |
| _version_ | 1826122837347270656 |
|---|---|
| author | Petros, Andrew M. Nettesheim, David G. Kim, Daniel H. Matayoshi, Edmund D. Fesik, Stephen W. Medek, Ales Yoon, Ho Sup Swift, Kerry Oltersdorf, Tilman |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Petros, Andrew M. Nettesheim, David G. Kim, Daniel H. Matayoshi, Edmund D. Fesik, Stephen W. Medek, Ales Yoon, Ho Sup Swift, Kerry Oltersdorf, Tilman |
| author_sort | Petros, Andrew M. |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T05:55:05Z |
| format | Conference Paper |
| id | ntu-10356/94051 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:55:05Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | ntu-10356/940512023-02-28T16:55:00Z Solution structure of the antiapoptotic protein bcl-2 Petros, Andrew M. Nettesheim, David G. Kim, Daniel H. Matayoshi, Edmund D. Fesik, Stephen W. Medek, Ales Yoon, Ho Sup Swift, Kerry Oltersdorf, Tilman School of Biological Sciences National Academy of Sciences (2001) DRNTU::Science::Biological sciences 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. Accepted version 2012-02-06T05:47:31Z 2019-12-06T18:49:58Z 2012-02-06T05:47:31Z 2019-12-06T18:49:58Z 2001 2001 Conference Paper 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. https://hdl.handle.net/10356/94051 http://hdl.handle.net/10220/7509 10.1073/pnas.041619798 11248023 en © 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 application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Petros, Andrew M. Nettesheim, David G. Kim, Daniel H. Matayoshi, Edmund D. Fesik, Stephen W. Medek, Ales Yoon, Ho Sup Swift, Kerry Oltersdorf, Tilman Solution structure of the antiapoptotic protein bcl-2 |
| title | Solution structure of the antiapoptotic protein bcl-2 |
| title_full | Solution structure of the antiapoptotic protein bcl-2 |
| title_fullStr | Solution structure of the antiapoptotic protein bcl-2 |
| title_full_unstemmed | Solution structure of the antiapoptotic protein bcl-2 |
| title_short | Solution structure of the antiapoptotic protein bcl-2 |
| title_sort | solution structure of the antiapoptotic protein bcl 2 |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/94051 http://hdl.handle.net/10220/7509 |
| work_keys_str_mv | AT petrosandrewm solutionstructureoftheantiapoptoticproteinbcl2 AT nettesheimdavidg solutionstructureoftheantiapoptoticproteinbcl2 AT kimdanielh solutionstructureoftheantiapoptoticproteinbcl2 AT matayoshiedmundd solutionstructureoftheantiapoptoticproteinbcl2 AT fesikstephenw solutionstructureoftheantiapoptoticproteinbcl2 AT medekales solutionstructureoftheantiapoptoticproteinbcl2 AT yoonhosup solutionstructureoftheantiapoptoticproteinbcl2 AT swiftkerry solutionstructureoftheantiapoptoticproteinbcl2 AT oltersdorftilman solutionstructureoftheantiapoptoticproteinbcl2 |