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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| Main Authors: | , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
2012
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/93655 http://hdl.handle.net/10220/7512 |
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| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | 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. |
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