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Biochemistry. 2011 May 3;50(17):3408-10. doi: 10.1021/bi2003247. Epub 2011 Apr 6.

Functional model of metabolite gating by human voltage-dependent anion channel 2.

Author information

1
Howard Hughes Medical Institute, Department of Biological Sciences, New York, New York 10027, United States.

Abstract

Voltage-dependent anion channels (VDACs) are critical regulators of outer mitochondrial membrane permeability in eukaryotic cells. VDACs have also been postulated to regulate cell death mechanisms. Erastin, a small molecule quinazolinone that is selectively lethal to tumor cells expressing mutant RAS, has previously been reported as a ligand for hVDAC2. While significant efforts have been made to elucidate the structure and function of hVDAC1, structural and functional characterization of hVDAC2 remains lacking. Here, we present an in vitro system that provides a platform for both functional and structural investigation of hVDAC2 and its small molecule modulator, erastin. Using this system, we found that erastin increases permeability of VDAC2 liposomes to NADH in a manner that requires the amino-terminal region of VDAC2. Furthermore, we confirmed that this VDAC2-lipsome sample is folded using solid-state NMR.

PMID:
21425834
PMCID:
PMC3082971
DOI:
10.1021/bi2003247
[Indexed for MEDLINE]
Free PMC Article

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