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The Protein Journal

, Volume 38, Issue 3, pp 306–316 | Cite as

Membrane Protein Integration and Topogenesis at the ER

  • Martin SpiessEmail author
  • Tina Junne
  • Marco Janoschke
Article

Abstract

Most membrane proteins are composed of hydrophobic α-helical transmembrane segments and are integrated into the lipid bilayer of the endoplasmic reticulum by the highly conserved Sec61 translocon. With respect to the integration mechanism, three types of transmembrane segments can be distinguished—the signal, the stop-transfer sequence, and the re-integration sequence—which in linear succession can account for all kinds of membrane protein topologies. The transmembrane orientation of the initial signal and to a weaker extent also of downstream transmembrane segments is affected by charged flanking residues according to the so-called positive-inside rule. The main driving force for transmembrane integration is hydrophobicity. Systematic analysis suggested thermodynamic equilibration of each peptide segment in the translocon with the membrane as the underlying mechanism. However, there is evidence that integration is not entirely sequence-autonomous, but depends also on the sequence context, from very closely spaced transmembrane segments to the folding state and properties of neighboring sequences. Topogenesis is even influenced by accessory proteins that appear to act as intramembrane chaperones.

Keywords

Sec61 Signal sequence Translocon Transmembrane helix 

Abbreviations

ER

Endoplasmic reticulum

Ncyt/Cexo

Cytoplasmic N- and exoplasmic C-terminus

Nexo/Ccyt

Exoplasmic N- and cytoplasmic C-terminus

TM

Transmembrane

TRAM

Translocating chain-associated membrane protein

Notes

Acknowledgements

Our work was supported by Grant No. 31003A-182519 from the Swiss National Science Foundation.

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Authors and Affiliations

  1. 1.BiozentrumUniversity of BaselBaselSwitzerland

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