Abstract
The hydrophobic core in Bcl-xL composed of Trp137, Ile140, Trp181, Ile182, Trp188 and Phe191 is highly conserved and essential for protein folding, protein stability and binding affinity with BH3-peptide. 9 mutants of Ile140 residue were constructed and characterized in order to get better understanding of the effect of the hydrophobic core. Binding assay demonstrated that binding affinities between 4 charged mutants and BH3-peptide were significantly weakened or lost, suggesting that the integrity of the hydrophobic core has close relationship with binding. The CD spectroscopy results indicated that disruption of the hydrophobic core may affect local conformation within the protein and result in intrinsic inactivity. Further chemical-induced protein folding results on these 4 mutants revealed that the conserved hydrophobic core is also important for the protein stability.
Keywords: Bad-BH3, Bcl-xL, binding, hydrophobic core, site-directed mutagenesis, stability
Protein & Peptide Letters
Title:Site-directed Mutagenesis Study of the Ile140 in Conserved Hydrophobic Core of Bcl-xL
Volume: 19 Issue: 9
Author(s): Xin Zhang, Ying Tan, Rui Zhao, Bizhu Chu, Chunyan Tan and Yuyang Jiang
Affiliation:
Keywords: Bad-BH3, Bcl-xL, binding, hydrophobic core, site-directed mutagenesis, stability
Abstract: The hydrophobic core in Bcl-xL composed of Trp137, Ile140, Trp181, Ile182, Trp188 and Phe191 is highly conserved and essential for protein folding, protein stability and binding affinity with BH3-peptide. 9 mutants of Ile140 residue were constructed and characterized in order to get better understanding of the effect of the hydrophobic core. Binding assay demonstrated that binding affinities between 4 charged mutants and BH3-peptide were significantly weakened or lost, suggesting that the integrity of the hydrophobic core has close relationship with binding. The CD spectroscopy results indicated that disruption of the hydrophobic core may affect local conformation within the protein and result in intrinsic inactivity. Further chemical-induced protein folding results on these 4 mutants revealed that the conserved hydrophobic core is also important for the protein stability.
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Cite this article as:
Zhang Xin, Tan Ying, Zhao Rui, Chu Bizhu, Tan Chunyan and Jiang Yuyang, Site-directed Mutagenesis Study of the Ile140 in Conserved Hydrophobic Core of Bcl-xL, Protein & Peptide Letters 2012; 19 (9) . https://dx.doi.org/10.2174/092986612802084500
DOI https://dx.doi.org/10.2174/092986612802084500 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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