---
_id: '8436'
abstract:
- lang: eng
  text: 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.
article_processing_charge: No
article_type: original
author:
- first_name: Katharina
  full_name: Weinhäupl, Katharina
  last_name: Weinhäupl
- first_name: Caroline
  full_name: Lindau, Caroline
  last_name: Lindau
- first_name: Audrey
  full_name: Hessel, Audrey
  last_name: Hessel
- first_name: Yong
  full_name: Wang, Yong
  last_name: Wang
- first_name: Conny
  full_name: Schütze, Conny
  last_name: Schütze
- first_name: Tobias
  full_name: Jores, Tobias
  last_name: Jores
- first_name: Laura
  full_name: Melchionda, Laura
  last_name: Melchionda
- first_name: Birgit
  full_name: Schönfisch, Birgit
  last_name: Schönfisch
- first_name: Hubert
  full_name: Kalbacher, Hubert
  last_name: Kalbacher
- first_name: Beate
  full_name: Bersch, Beate
  last_name: Bersch
- first_name: Doron
  full_name: Rapaport, Doron
  last_name: Rapaport
- first_name: Martha
  full_name: Brennich, Martha
  last_name: Brennich
- first_name: Kresten
  full_name: Lindorff-Larsen, Kresten
  last_name: Lindorff-Larsen
- first_name: Nils
  full_name: Wiedemann, Nils
  last_name: Wiedemann
- first_name: Paul
  full_name: Schanda, Paul
  id: 7B541462-FAF6-11E9-A490-E8DFE5697425
  last_name: Schanda
  orcid: 0000-0002-9350-7606
citation:
  ama: Weinhäupl K, Lindau C, Hessel A, et al. Structural basis of membrane protein
    chaperoning through the mitochondrial intermembrane space. <i>Cell</i>. 2018;175(5):1365-1379.e25.
    doi:<a href="https://doi.org/10.1016/j.cell.2018.10.039">10.1016/j.cell.2018.10.039</a>
  apa: 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. <i>Cell</i>. Elsevier. <a href="https://doi.org/10.1016/j.cell.2018.10.039">https://doi.org/10.1016/j.cell.2018.10.039</a>
  chicago: 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.” <i>Cell</i>.
    Elsevier, 2018. <a href="https://doi.org/10.1016/j.cell.2018.10.039">https://doi.org/10.1016/j.cell.2018.10.039</a>.
  ieee: K. Weinhäupl <i>et al.</i>, “Structural basis of membrane protein chaperoning
    through the mitochondrial intermembrane space,” <i>Cell</i>, vol. 175, no. 5.
    Elsevier, p. 1365–1379.e25, 2018.
  ista: 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.
  mla: Weinhäupl, Katharina, et al. “Structural Basis of Membrane Protein Chaperoning
    through the Mitochondrial Intermembrane Space.” <i>Cell</i>, vol. 175, no. 5,
    Elsevier, 2018, p. 1365–1379.e25, doi:<a href="https://doi.org/10.1016/j.cell.2018.10.039">10.1016/j.cell.2018.10.039</a>.
  short: K. Weinhäupl, C. Lindau, A. Hessel, Y. Wang, C. Schütze, T. Jores, L. Melchionda,
    B. Schönfisch, H. Kalbacher, B. Bersch, D. Rapaport, M. Brennich, K. Lindorff-Larsen,
    N. Wiedemann, P. Schanda, Cell 175 (2018) 1365–1379.e25.
date_created: 2020-09-18T10:04:39Z
date_published: 2018-11-15T00:00:00Z
date_updated: 2021-01-12T08:19:15Z
day: '15'
doi: 10.1016/j.cell.2018.10.039
extern: '1'
intvolume: '       175'
issue: '5'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '11'
oa_version: None
page: 1365-1379.e25
publication: Cell
publication_identifier:
  issn:
  - 0092-8674
publication_status: published
publisher: Elsevier
quality_controlled: '1'
status: public
title: Structural basis of membrane protein chaperoning through the mitochondrial
  intermembrane space
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 175
year: '2018'
...