Academic Appointments

Professional Education

  • B.Sc., University of Leipzig, Biochemistry (2010)
  • M.Sc., Georg-August-University Göttingen (Max Planck Institute for Multidisciplinary Sciences), Molecular Biology (2012)
  • PhD, Georg-August-University Göttingen (Max Planck Institute for Multidisciplinary Sciences), Molecular Biology (2016)

Current Research and Scholarly Interests

The Pleiner lab combines mechanistic cell biology, structural biochemistry and protein engineering to dissect the pathways and molecular machines that mature human membrane proteins to a fully functional state. We also develop alpaca-derived and synthetic nanobodies as tools to modulate intracellular pathways that globally regulate protein homeostasis in health and disease.

All Publications

  • A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER JOURNAL OF CELL BIOLOGY Pleiner, T., Hazu, M., Tomaleri, G., Nguyen, V. N., Januszyk, K., Voorhees, R. M. 2023; 222 (8)


    Tail-anchored (TA) proteins play essential roles in mammalian cells, and their accurate localization is critical for proteostasis. Biophysical similarities lead to mistargeting of mitochondrial TA proteins to the ER, where they are delivered to the insertase, the ER membrane protein complex (EMC). Leveraging an improved structural model of the human EMC, we used mutagenesis and site-specific crosslinking to map the path of a TA protein from its cytosolic capture by methionine-rich loops to its membrane insertion through a hydrophilic vestibule. Positively charged residues at the entrance to the vestibule function as a selectivity filter that uses charge-repulsion to reject mitochondrial TA proteins. Similarly, this selectivity filter retains the positively charged soluble domains of multipass substrates in the cytosol, thereby ensuring they adopt the correct topology and enforcing the "positive-inside" rule. Substrate discrimination by the EMC provides a biochemical explanation for one role of charge in TA protein sorting and protects compartment integrity by limiting protein misinsertion.

    View details for DOI 10.1083/jcb.202212007

    View details for Web of Science ID 001006684400001

    View details for PubMedID 37199759

    View details for PubMedCentralID PMC10200711