beta-Barrel Mobility Underlies Closure of the Voltage-Dependent Anion Channel
2012 | journal article; research paper. A publication with affiliation to the University of Göttingen.
Jump to: Cite & Linked | Documents & Media | Details | Version history
Documents & Media
Details
- Authors
- Zachariae, Ulrich; Schneider, Robert ; Briones, Rodolfo ; Gattin, Zrinka ; Demers, Jean-Philippe; Giller, Karin ; Maier, Elke; Zweckstetter, Markus ; Griesinger, Christian ; Becker, Stefan ; Benz, Roland; Groot, Bert L. de ; Lange, Adam
- Abstract
- The voltage-dependent anion channel (VDAC) is the major protein in the outer mitochondrial membrane, where it mediates transport of ATP and ADP. Changes in its permeability, induced by voltage or apoptosis-related proteins, have been implicated in apoptotic pathways. The three-dimensional structure of VDAC has recently been determined as a 19-stranded beta-barrel with an in-lying N-terminal helix. However, its gating mechanism is still unclear. Using solid-state NMR spectroscopy, molecular dynamics simulations, and electrophysiology, we show that deletion of the rigid N-terminal helix sharply increases overall motion in VDAC's beta-barrel, resulting in elliptic, semicollapsed barrel shapes. These states quantitatively reproduce conductance and selectivity of the closed VDAC conformation. Mutation of the N-terminal helix leads to a phenotype intermediate to the open and closed states. These data suggest that the N-terminal helix controls entry into elliptic beta-barrel states which underlie VDAC closure. Our results also indicate that beta-barrel channels are intrinsically flexible.
- Issue Date
- 2012
- Publisher
- Cell Press
- Journal
- Structure
- ISSN
- 0969-2126
- eISSN
- 1878-4186