TRAP assists membrane protein topogenesis at the mammalian ER membrane

Nicole Sommer*, Tina Junne, Kai Uwe Kalies, Martin Spiess, Enno Hartmann

*Corresponding author for this work
19 Citations (Scopus)


Membrane protein insertion and topogenesis generally occur at the Sec61 translocon in the endoplasmic reticulum membrane. During this process, membrane spanning segments may adopt two distinct orientations with either their N- or C-terminus translocated into the ER lumen. While different topogenic determinants in membrane proteins, such as flanking charges, polypeptide folding, and hydrophobicity, have been identified, it is not well understood how the translocon and/or associated components decode them. Here we present evidence that the translocon-associated protein (TRAP) complex is involved in membrane protein topogenesis in vivo. Small interfering RNA (siRNA)-mediated silencing of the TRAP complex in HeLa cells enhanced the topology effect of mutating the flanking charges of a signal-anchor, but not of increasing signal hydrophobicity. The results suggest a role of the TRAP complex in moderating the 'positive-inside' rule.

Original languageEnglish
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number12
Pages (from-to)3104-3111
Number of pages8
Publication statusPublished - 01.12.2013


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