Molecular basis of the TRAP complex function in ER protein biogenesis

Nat Struct Mol Biol. 2023 Jun;30(6):770-777. doi: 10.1038/s41594-023-00990-0. Epub 2023 May 11.


The translocon-associated protein (TRAP) complex resides in the endoplasmic reticulum (ER) membrane and interacts with the Sec translocon and the ribosome to facilitate biogenesis of secretory and membrane proteins. TRAP plays a key role in the secretion of many hormones, including insulin. Here we reveal the molecular architecture of the mammalian TRAP complex and how it engages the translating ribosome associated with Sec61 translocon on the ER membrane. The TRAP complex is anchored to the ribosome via a long tether and its position is further stabilized by a finger-like loop. This positions a cradle-like lumenal domain of TRAP below the translocon for interactions with translocated nascent chains. Our structure-guided TRAP mutations in Caenorhabditis elegans lead to growth deficits associated with increased ER stress and defects in protein hormone secretion. These findings elucidate the molecular basis of the TRAP complex in the biogenesis and translocation of proteins at the ER.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins / metabolism
  • Endoplasmic Reticulum* / metabolism
  • Mammals / metabolism
  • Membrane Glycoproteins* / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Protein Transport
  • SEC Translocation Channels / metabolism


  • signal sequence receptor
  • Membrane Glycoproteins
  • Calcium-Binding Proteins
  • Membrane Proteins
  • SEC Translocation Channels