Journal Article

DZNE-2020-04798

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Molecular Plasticity of the Human Voltage-Dependent Anion Channel Embedded Into a Membrane.

Ge, L. ; Villinger, S. ; Mari, S. A. ; Giller, K. ; Griesinger, C. ; Becker, S. ; Müller, D. J. (Corresponding author) ; Zweckstetter, M. (Last author)DZNE*

2016
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: doi:10.1016/j.str.2016.02.012

Abstract: The voltage-dependent anion channel (VDAC) regulates the flux of metabolites and ions across the outer mitochondrial membrane. Regulation of ion flow involves conformational transitions in VDAC, but the nature of these changes has not been resolved to date. By combining single-molecule force spectroscopy with nuclear magnetic resonance spectroscopy we show that the β barrel of human VDAC embedded into a membrane is highly flexible. Its mechanical flexibility exceeds by up to one order of magnitude that determined for β strands of other membrane proteins and is largest in the N-terminal part of the β barrel. Interaction with Ca(2+), a key regulator of metabolism and apoptosis, considerably decreases the barrel's conformational variability and kinetic free energy in the membrane. The combined data suggest that physiological VDAC function depends on the molecular plasticity of its channel.

Keyword(s): Calcium: metabolism (MeSH) ; Humans (MeSH) ; Kinetics (MeSH) ; Mitochondrial Membranes: metabolism (MeSH) ; Models, Molecular (MeSH) ; Nuclear Magnetic Resonance, Biomolecular (MeSH) ; Protein Structure, Secondary (MeSH) ; Single Molecule Imaging (MeSH) ; Voltage-Dependent Anion Channel 1: chemistry (MeSH) ; Voltage-Dependent Anion Channel 1: metabolism (MeSH) ; VDAC1 protein, human ; Voltage-Dependent Anion Channel 1 ; Calcium

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Contributing Institute(s):

1. Structural Biology in Dementia (AG Zweckstetter)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2016

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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