Oligomerization of BH4-truncated Bcl-xL in solution

Youli Wang; Rong Cao; Dongxiang Liu; Adam Chervin; Jian Yuan; Jing An; Ziwei Huang

doi:10.1016/j.bbrc.2007.07.122

Oligomerization of BH4-truncated Bcl-x_L in solution

Youli Wang, Rong Cao, Dongxiang Liu, Adam Chervin, Jian Yuan, Jing An, Ziwei Huang

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

BH4 domain is critical for the anti-apoptotic functions of Bcl-2 and Bcl-x_L and their binding abilities with other members of the Bcl-2 family. The cleavage of the BH4 domain in Bcl-x_L and Bcl-2 by caspase 1 or 3 converts the anti-apoptotic Bcl-x_L and Bcl-2 into pro-apoptotic proteins that potently induce apoptosis. Herein, we report that recombinant Bcl-x_L proteins without N-terminal 61 residues, His₆-NΔ61-Bcl-x_L-CΔ21 and NΔ61-Bcl-x_L-CΔ21, form oligomers in solution, whereas Bcl-x_L-CΔ21 exists as a monomer. The oligomerization of the truncated proteins is independent of protein-lipid interaction, protein concentration or the ion strength of the solution. Circular dichroism spectrum shows a significant decrease in the content of α-helices upon deletion of N-terminal residues. NΔ61-Bcl-x_L-CΔ21 also loses its heterodimerization capability with the BH3 peptide derived from Bak. This newly acquired property might be linked to its ability to induce apoptosis in cells.

Original language	English (US)
Pages (from-to)	1006-1011
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	361
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2007.07.122
State	Published - Oct 5 2007
Externally published	Yes

Keywords

Apoptosis
BH4 domain
Bcl-2
Bcl-x
Oligomerization
Truncated Bcl-x

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2007.07.122

Cite this

@article{73d8464af8fd4904923405cf446b02b5,

title = "Oligomerization of BH4-truncated Bcl-xL in solution",

abstract = "BH4 domain is critical for the anti-apoptotic functions of Bcl-2 and Bcl-xL and their binding abilities with other members of the Bcl-2 family. The cleavage of the BH4 domain in Bcl-xL and Bcl-2 by caspase 1 or 3 converts the anti-apoptotic Bcl-xL and Bcl-2 into pro-apoptotic proteins that potently induce apoptosis. Herein, we report that recombinant Bcl-xL proteins without N-terminal 61 residues, His6-NΔ61-Bcl-xL-CΔ21 and NΔ61-Bcl-xL-CΔ21, form oligomers in solution, whereas Bcl-xL-CΔ21 exists as a monomer. The oligomerization of the truncated proteins is independent of protein-lipid interaction, protein concentration or the ion strength of the solution. Circular dichroism spectrum shows a significant decrease in the content of α-helices upon deletion of N-terminal residues. NΔ61-Bcl-xL-CΔ21 also loses its heterodimerization capability with the BH3 peptide derived from Bak. This newly acquired property might be linked to its ability to induce apoptosis in cells.",

keywords = "Apoptosis, BH4 domain, Bcl-2, Bcl-x, Oligomerization, Truncated Bcl-x",

author = "Youli Wang and Rong Cao and Dongxiang Liu and Adam Chervin and Jian Yuan and Jing An and Ziwei Huang",

note = "Funding Information: We thank Amy Balija for the technical assistance of DLS. This work was supported by grants from the NIH and American Cancer Society.",

year = "2007",

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T1 - Oligomerization of BH4-truncated Bcl-xL in solution

AU - Wang, Youli

AU - Cao, Rong

AU - Liu, Dongxiang

AU - Chervin, Adam

AU - Yuan, Jian

AU - An, Jing

AU - Huang, Ziwei

N1 - Funding Information: We thank Amy Balija for the technical assistance of DLS. This work was supported by grants from the NIH and American Cancer Society.

PY - 2007/10/5

Y1 - 2007/10/5

N2 - BH4 domain is critical for the anti-apoptotic functions of Bcl-2 and Bcl-xL and their binding abilities with other members of the Bcl-2 family. The cleavage of the BH4 domain in Bcl-xL and Bcl-2 by caspase 1 or 3 converts the anti-apoptotic Bcl-xL and Bcl-2 into pro-apoptotic proteins that potently induce apoptosis. Herein, we report that recombinant Bcl-xL proteins without N-terminal 61 residues, His6-NΔ61-Bcl-xL-CΔ21 and NΔ61-Bcl-xL-CΔ21, form oligomers in solution, whereas Bcl-xL-CΔ21 exists as a monomer. The oligomerization of the truncated proteins is independent of protein-lipid interaction, protein concentration or the ion strength of the solution. Circular dichroism spectrum shows a significant decrease in the content of α-helices upon deletion of N-terminal residues. NΔ61-Bcl-xL-CΔ21 also loses its heterodimerization capability with the BH3 peptide derived from Bak. This newly acquired property might be linked to its ability to induce apoptosis in cells.

AB - BH4 domain is critical for the anti-apoptotic functions of Bcl-2 and Bcl-xL and their binding abilities with other members of the Bcl-2 family. The cleavage of the BH4 domain in Bcl-xL and Bcl-2 by caspase 1 or 3 converts the anti-apoptotic Bcl-xL and Bcl-2 into pro-apoptotic proteins that potently induce apoptosis. Herein, we report that recombinant Bcl-xL proteins without N-terminal 61 residues, His6-NΔ61-Bcl-xL-CΔ21 and NΔ61-Bcl-xL-CΔ21, form oligomers in solution, whereas Bcl-xL-CΔ21 exists as a monomer. The oligomerization of the truncated proteins is independent of protein-lipid interaction, protein concentration or the ion strength of the solution. Circular dichroism spectrum shows a significant decrease in the content of α-helices upon deletion of N-terminal residues. NΔ61-Bcl-xL-CΔ21 also loses its heterodimerization capability with the BH3 peptide derived from Bak. This newly acquired property might be linked to its ability to induce apoptosis in cells.

KW - Apoptosis

KW - BH4 domain

KW - Bcl-2

KW - Bcl-x

KW - Oligomerization

KW - Truncated Bcl-x

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