NMR structural investigation of the mitochondrial outer membrane protein VDAC and its interaction with antiapoptotic Bcl-xL.

NMR structural investigation of the mitochondrial outer membrane protein VDAC and its interaction with antiapoptotic Bcl-xL. Research Abstract Details 

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NMR structural investigation of the mitochondrial outer membrane protein VDAC and its interaction with antiapoptotic Bcl-xL. Abstract Text:

Thomas J Malia,Gerhard Wagner,

Bcl-2 family proteins are essential regulators of cell death and exert their primary pro- or antiapoptotic roles at the mitochondrial outer membrane. Previously, pro- and antiapoptotic Bcl-2 proteins have been shown to interact with the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. VDAC is a 283-residue integral membrane protein that forms an aqueous pore in the outer mitochondrial membrane, through which metabolites and other small molecules pass between the cytosol and intermembrane space. The essential life-sustaining function of VDAC in metabolite trafficking is believed to be regulated by proteins of the Bcl-2 family. The protective role of antiapoptotic Bcl-xL may be through its interaction with VDAC. Here, VDAC has been expressed, purified, and refolded into a functional form amenable to NMR studies. Various biophysical experiments indicate that micelle-bound VDAC is in intermediate exchange between monomer and trimer. Using NMR spectroscopy, gel filtration, and chemical cross-linking, we obtained direct evidence for binding of Bcl-xL to VDAC in a detergent micelle system. The VDAC-interacting region of Bcl-xL was characterized by NMR with chemical shift perturbation and transferred cross-saturation. The interaction region was mapped to a putative helical hairpin motif of Bcl-xL that was found to insert into detergent micelles. Our results suggest that Bcl-xL can bind to one or two VDAC molecules forming heterodimers and heterotrimers. Our characterization of the VDAC/Bcl-xL complex offers initial structural insight into the role of antiapoptotic Bcl-xL in regulating apoptotic events in the mitochondrial outer membrane.

NMR structural investigation of the mitochondrial outer membrane protein VDAC and its interaction with antiapoptotic Bcl-xL. Publishing Authors By Initials

TJ Malia,G Wagner,

For similar peptides: intracellular signaling peptides and proteins: apoptosis regulatory proteins: proto-oncogene proteins c-bcl-2: bcl-x protein research abstracts see: peptides: intracellular signaling peptides and proteins: apoptosis regulatory proteins: proto-oncogene proteins c-bcl-2: bcl-x protein research

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NMR structural investigation of the mitochondrial outer membrane protein VDAC and its interaction with antiapoptotic Bcl-xL. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Biochemistry

VOLUME: 46

Page Numbers: 514-25

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 16

MONTH: Jan

YEAR: 2007

NMR structural investigation of the mitochondrial outer membrane protein VDAC and its interaction with antiapoptotic Bcl-xL. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370623

NMR structural investigation of the mitochondrial outer membrane protein VDAC and its interaction with antiapoptotic Bcl-xL. Keywords Mesh Terms:

KEYWORDS: bcl-X Protein

MESH TERMS: metabolism

Chemical & Substance for Abstract: NMR structural investigation of the mitochondrial outer membrane protein VDAC and its interaction with antiapoptotic Bcl-xL. Information

Substance Name: Voltage-Dependent Anion Channel 1

Registry Number: EC 1.6.-

Grant and Affiliation Information for NMR structural investigation of the mitochondrial outer membrane protein VDAC and its interaction with antiapoptotic Bcl-xL.

AFFILIATION: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM075879

ACRONYM: GM

MEDLINETA: Biochemistry

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