A Conserved Archaeal Pathway for Tail-Anchored Membrane Protein Insertion

Authors

  • John Sherrill,

    1. Department of Biochemistry & Molecular Biology, University of Chicago, Gordon Center for Integrative Science, Room W238, Chicago, IL 60637, USA
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  • Malaiyalam Mariappan,

    1. Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Room 101, Building 18T, 18 Library Drive, Bethesda, MD 20892, USA
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  • Pawel Dominik,

    1. Department of Biochemistry & Molecular Biology, University of Chicago, Gordon Center for Integrative Science, Room W238, Chicago, IL 60637, USA
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  • Ramanujan S. Hegde,

    1. Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Room 101, Building 18T, 18 Library Drive, Bethesda, MD 20892, USA
    2. Present address: MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, United Kingdom
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  • Robert J. Keenan

    Corresponding author
    1. Department of Biochemistry & Molecular Biology, University of Chicago, Gordon Center for Integrative Science, Room W238, Chicago, IL 60637, USA
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Robert J. Keenan, bkeenan@uchicago.edu

Abstract

Eukaryotic tail-anchored (TA) membrane proteins are inserted into the endoplasmic reticulum by a post-translational TRC40 pathway, but no comparable pathway is known in other domains of life. The crystal structure of an archaebacterial TRC40 sequence homolog bound to ADP•AlF4 reveals characteristic features of eukaryotic TRC40, including a zinc-mediated dimer and a large hydrophobic groove. Moreover, archaeal TRC40 interacts with the transmembrane domain of TA substrates and directs their membrane insertion. Thus, the TRC40 pathway is more broadly conserved than previously recognized.

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