Open AccessDissecting the molecular organization of the translocon-associated protein complex
Author(s) -
Stefan Pfeffer,
Johanna Dudek,
Miroslava Schaffer,
Bobby G. Ng,
Sahradha Albert,
Jürgen M. Plitzko,
Wolfgang Baumeister,
Richard Zimmermann,
Hudson H. Freeze,
Benjamin D. Engel,
Friedrich Förster
Publication year - 2017
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms14516
Subject(s) - translocon , sec61 , endoplasmic reticulum , biogenesis , transmembrane protein , microbiology and biotechnology , trap (plumbing) , signal peptide , biology , membrane protein , peptide sequence , genetics , membrane , physics , receptor , meteorology , gene
In eukaryotic cells, one-third of all proteins must be transported across or inserted into the endoplasmic reticulum (ER) membrane by the ER protein translocon. The translocon-associated protein (TRAP) complex is an integral component of the translocon, assisting the Sec61 protein-conducting channel by regulating signal sequence and transmembrane helix insertion in a substrate-dependent manner. Here we use cryo-electron tomography (CET) to study the structure of the native translocon in evolutionarily divergent organisms and disease-linked TRAP mutant fibroblasts from human patients. The structural differences detected by subtomogram analysis form a basis for dissecting the molecular organization of the TRAP complex. We assign positions to the four TRAP subunits within the complex, providing insights into their individual functions. The revealed molecular architecture of a central translocon component advances our understanding of membrane protein biogenesis and sheds light on the role of TRAP in human congenital disorders of glycosylation.