Details

Autor(en) / Beteiligte

• Villinger, Saskia
• Briones, Rodolfo
• Giller, Karin
• Zachariae, Ulrich
• Lange, Adam
• de Groot, Bert L.
• Griesinger, Christian
• Becker, Stefan
• Zweckstetter, Markus
• Gouaux, Eric

Titel

Functional dynamics in the voltage-dependent anion channel

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2010-12, Vol.107 (52), p.22546-22551

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 β-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.