Structural basis of membrane protein chaperoning through the mitochondrial intermembrane space

Weinhäupl K, Lindau C, Hessel A, Wang Y, Schütze C, Jores T, Melchionda L, Schönfisch B, Kalbacher H, Bersch B, Rapaport D, Brennich M, Lindorff-Larsen K, Wiedemann N, Schanda P. 2018. Structural basis of membrane protein chaperoning through the mitochondrial intermembrane space. Cell. 175(5), 1365–1379.e25.

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Journal Article | Published | English
Author
Weinhäupl, Katharina; Lindau, Caroline; Hessel, Audrey; Wang, Yong; Schütze, Conny; Jores, Tobias; Melchionda, Laura; Schönfisch, Birgit; Kalbacher, Hubert; Bersch, Beate; Rapaport, Doron; Brennich, Martha
All
Abstract
The exchange of metabolites between the mitochondrial matrix and the cytosol depends on β-barrel channels in the outer membrane and α-helical carrier proteins in the inner membrane. The essential translocase of the inner membrane (TIM) chaperones escort these proteins through the intermembrane space, but the structural and mechanistic details remain elusive. We have used an integrated structural biology approach to reveal the functional principle of TIM chaperones. Multiple clamp-like binding sites hold the mitochondrial membrane proteins in a translocation-competent elongated form, thus mimicking characteristics of co-translational membrane insertion. The bound preprotein undergoes conformational dynamics within the chaperone binding clefts, pointing to a multitude of dynamic local binding events. Mutations in these binding sites cause cell death or growth defects associated with impairment of carrier and β-barrel protein biogenesis. Our work reveals how a single mitochondrial “transfer-chaperone” system is able to guide α-helical and β-barrel membrane proteins in a “nascent chain-like” conformation through a ribosome-free compartment.
Publishing Year
Date Published
2018-11-15
Journal Title
Cell
Volume
175
Issue
5
Page
1365-1379.e25
ISSN
IST-REx-ID

Cite this

Weinhäupl K, Lindau C, Hessel A, et al. Structural basis of membrane protein chaperoning through the mitochondrial intermembrane space. Cell. 2018;175(5):1365-1379.e25. doi:10.1016/j.cell.2018.10.039
Weinhäupl, K., Lindau, C., Hessel, A., Wang, Y., Schütze, C., Jores, T., … Schanda, P. (2018). Structural basis of membrane protein chaperoning through the mitochondrial intermembrane space. Cell. Elsevier. https://doi.org/10.1016/j.cell.2018.10.039
Weinhäupl, Katharina, Caroline Lindau, Audrey Hessel, Yong Wang, Conny Schütze, Tobias Jores, Laura Melchionda, et al. “Structural Basis of Membrane Protein Chaperoning through the Mitochondrial Intermembrane Space.” Cell. Elsevier, 2018. https://doi.org/10.1016/j.cell.2018.10.039.
K. Weinhäupl et al., “Structural basis of membrane protein chaperoning through the mitochondrial intermembrane space,” Cell, vol. 175, no. 5. Elsevier, p. 1365–1379.e25, 2018.
Weinhäupl K, Lindau C, Hessel A, Wang Y, Schütze C, Jores T, Melchionda L, Schönfisch B, Kalbacher H, Bersch B, Rapaport D, Brennich M, Lindorff-Larsen K, Wiedemann N, Schanda P. 2018. Structural basis of membrane protein chaperoning through the mitochondrial intermembrane space. Cell. 175(5), 1365–1379.e25.
Weinhäupl, Katharina, et al. “Structural Basis of Membrane Protein Chaperoning through the Mitochondrial Intermembrane Space.” Cell, vol. 175, no. 5, Elsevier, 2018, p. 1365–1379.e25, doi:10.1016/j.cell.2018.10.039.

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