Molecular basis of Bcl-XL-p53 interaction : insights from molecular dynamics simulations
Bcl-XL, an antiapoptotic Bcl-2 family protein, plays a central role in the regulation of the apoptotic pathway. Heterodimerization of the antiapoptotic Bcl-2 family proteins with the proapoptotic family members such as Bad, Bak, Bim and Bid is a crucial step in the apoptotic regulation. In add...
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| Format: | Journal Article |
| Language: | English |
| Published: |
2012
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| Online Access: | https://hdl.handle.net/10356/93655 http://hdl.handle.net/10220/7512 |
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| author | Bharatham, Nagakumar Chi, Seung-Wook Yoon, Ho Sup |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Bharatham, Nagakumar Chi, Seung-Wook Yoon, Ho Sup |
| author_sort | Bharatham, Nagakumar |
| collection | NTU |
| description | Bcl-XL, an antiapoptotic Bcl-2 family protein, plays a central role in the regulation of the apoptotic pathway.
Heterodimerization of the antiapoptotic Bcl-2 family proteins with the proapoptotic family members such as Bad, Bak,
Bim and Bid is a crucial step in the apoptotic regulation. In addition to these conventional binding partners, recent
evidences reveal that the Bcl-2 family proteins also interact with noncanonical binding partners such as p53. Our previous
NMR studies showed that Bcl-XL: BH3 peptide and Bcl-XL: SN15 peptide (a peptide derived from residues S15-N29 of p53)
complex structures share similar modes of bindings. To further elucidate the molecular basis of the interactions, here we
have employed molecular dynamics simulations coupled with MM/PBSA approach. Bcl-XL and other Bcl-2 family proteins
have 4 hydrophobic pockets (p1–p4), which are occupied by four systematically spaced hydrophobic residues (h1–h4) of
the proapoptotic Bad and Bak BH3 peptides. We observed that three conserved hydrophobic residues (F19, W23 and L26) of
p53 (SN15) peptide anchor into three hydrophobic pockets (p2–p4) of Bcl-XL in a similar manner as BH3 peptide. Our results
provide insights into the novel molecular recognition by Bcl-XL with p53. |
| first_indexed | 2024-10-01T05:25:19Z |
| format | Journal Article |
| id | ntu-10356/93655 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:25:19Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | ntu-10356/936552023-02-28T17:03:43Z Molecular basis of Bcl-XL-p53 interaction : insights from molecular dynamics simulations Bharatham, Nagakumar Chi, Seung-Wook Yoon, Ho Sup School of Biological Sciences DRNTU::Science::Biological sciences Bcl-XL, an antiapoptotic Bcl-2 family protein, plays a central role in the regulation of the apoptotic pathway. Heterodimerization of the antiapoptotic Bcl-2 family proteins with the proapoptotic family members such as Bad, Bak, Bim and Bid is a crucial step in the apoptotic regulation. In addition to these conventional binding partners, recent evidences reveal that the Bcl-2 family proteins also interact with noncanonical binding partners such as p53. Our previous NMR studies showed that Bcl-XL: BH3 peptide and Bcl-XL: SN15 peptide (a peptide derived from residues S15-N29 of p53) complex structures share similar modes of bindings. To further elucidate the molecular basis of the interactions, here we have employed molecular dynamics simulations coupled with MM/PBSA approach. Bcl-XL and other Bcl-2 family proteins have 4 hydrophobic pockets (p1–p4), which are occupied by four systematically spaced hydrophobic residues (h1–h4) of the proapoptotic Bad and Bak BH3 peptides. We observed that three conserved hydrophobic residues (F19, W23 and L26) of p53 (SN15) peptide anchor into three hydrophobic pockets (p2–p4) of Bcl-XL in a similar manner as BH3 peptide. Our results provide insights into the novel molecular recognition by Bcl-XL with p53. Published version 2012-02-07T03:28:51Z 2019-12-06T18:43:06Z 2012-02-07T03:28:51Z 2019-12-06T18:43:06Z 2011 2011 Journal Article Bharatham, N., Chi S. W., Yoon, H. S. (2011). Molecular Basis of Bcl-XL-p53 Interaction: Insights from Molecular Dynamics Simulations. PLoS ONE, 6(10), 1-12. https://hdl.handle.net/10356/93655 http://hdl.handle.net/10220/7512 10.1371/journal.pone.0026014 22039431 en PLoS one © 2011 The authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 12 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Bharatham, Nagakumar Chi, Seung-Wook Yoon, Ho Sup Molecular basis of Bcl-XL-p53 interaction : insights from molecular dynamics simulations |
| title | Molecular basis of Bcl-XL-p53 interaction : insights from molecular dynamics simulations |
| title_full | Molecular basis of Bcl-XL-p53 interaction : insights from molecular dynamics simulations |
| title_fullStr | Molecular basis of Bcl-XL-p53 interaction : insights from molecular dynamics simulations |
| title_full_unstemmed | Molecular basis of Bcl-XL-p53 interaction : insights from molecular dynamics simulations |
| title_short | Molecular basis of Bcl-XL-p53 interaction : insights from molecular dynamics simulations |
| title_sort | molecular basis of bcl xl p53 interaction insights from molecular dynamics simulations |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/93655 http://hdl.handle.net/10220/7512 |
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