Functional dynamics in the voltage-dependent anion channel
2010 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Functional dynamics in the voltage-dependent anion channel
Villinger, S. ; Briones, R. ; Giller, K. ; Zachariae, U.; Lange, A. ; Groot, B. L. de & Griesinger, C. et al. (2010)
Proceedings of the National Academy of Sciences, 107(52) pp. 22546-22551. DOI: https://doi.org/10.1073/pnas.1012310108
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- Authors
- Villinger, Saskia ; Briones, Rodolfo ; Giller, Karin ; Zachariae, Ulrich; Lange, Adam ; Groot, Bert L. de ; Griesinger, Christian ; Becker, Stefan ; Zweckstetter, Markus
- Abstract
- The voltage-dependent anion channel (VDAC), located in the outer mitochondrial membrane, acts as a gatekeeper for the entry and exit of mitochondrial metabolites. Here we reveal functional dynamics of isoform one of VDAC (VDAC1) by a combination of solution NMR spectroscopy, Gaussian network model analysis, and molecular dynamics simulation. Micro-to millisecond dynamics are significantly increased for the N-terminal six beta-strands of VDAC1 in micellar solution, in agreement with increased B-factors observed in the same region in the bicellar crystal structure of VDAC1. Molecular dynamics simulations reveal that a charge on the membrane-facing glutamic acid 73 (E73) accounts for the elevation of N-terminal protein dynamics as well as a thinning of the nearby membrane. Mutation or chemical modification of E73 strongly reduces the micro-to millisecond dynamics in solution. Because E73 is necessary for hexokinase-I-induced VDAC channel closure and inhibition of apoptosis, our results imply that micro- to millisecond dynamics in the N-terminal part of the barrel are essential for VDAC interaction and gating.
- Issue Date
- 2010
- Publisher
- Natl Acad Sciences
- Journal
- Proceedings of the National Academy of Sciences
- ISSN
- 0027-8424