The EMC acts as a chaperone for membrane proteins.

Journal: Nature communications
Published Date: Aug 2, 2025

Abstract

Structure formation of membrane proteins is error-prone and thus requires chaperones that oversee this essential process in cell biology. The ER membrane protein complex (EMC) is well-defined as a transmembrane domain (TMD) insertase. In this study, we characterize an additional chaperone function of the EMC. We use interactomics and systematic studies with model proteins to comprehensively define client features for this EMC chaperone mode. Based on this data, we develop a machine learning-based tool for client prediction. Mechanistically, our study reveals that the EMC engages TMDs via its EMC1 subunit and modulates their orientation within the lipid bilayer. Productive TMD assembly reduces binding to the EMC chaperone site. Taken together, our study provides detailed insights into an EMC chaperone function, further establishing the role of the EMC as a multifunctional molecular machine in membrane protein biogenesis.

Authors

  • Carolin J Klose
    Department of Bioscience, TUM School of Natural Sciences, Center for Functional Protein Assemblies (CPA), Technical University of Munich, Garching, Germany.
  • Kevin M Meighen-Berger
    Department of Bioscience, TUM School of Natural Sciences, Center for Functional Protein Assemblies (CPA), Technical University of Munich, Garching, Germany.
  • Martin Kulke
    Department of Bioscience, TUM School of Natural Sciences, Center for Functional Protein Assemblies (CPA), Technical University of Munich, Garching, Germany.
  • Marina Parr
    Department of Bioinformatics, Wissenschaftszentrum Weihenstephan, Technical University of Munich, Freising, Germany.
  • Barbara Steigenberger
    Mass Spectrometry Core Facility, Max Planck Institute of Biochemistry, Martinsried, Germany.
  • Martin Zacharias
    Physik Department T38, Technische Universität München, James-Franck-Straße, Garching, Germany.
  • Dmitrij Frishman
    Department of Bioinformatics, Technische Universität München, Wissenschaftszentrum Weihenstephan, Freising, Germany.
  • Matthias J Feige
    Department of Bioscience, TUM School of Natural Sciences, Center for Functional Protein Assemblies (CPA), Technical University of Munich, Garching, Germany. Matthias.Feige@tum.de.

Keywords

External Resources

Popular Topics
Recent Journals