Folding and insertion of transmembrane helices at the ER

Paul Whitley, Brayan Grau, James C. Gumbart, Luis Martínez-Gil, Ismael Mingarro

Research output: Contribution to journalReview articlepeer-review

2 Citations (SciVal)


In eukaryotic cells, the endoplasmic reticulum (ER) is the entry point for newly synthesized proteins that are subsequently distributed to organelles of the endomembrane system. Some of these proteins are completely translocated into the lumen of the ER while others integrate stretches of amino acids into the greasy 30 Å wide interior of the ER membrane bilayer. It is generally accepted that to exist in this non-aqueous environment the majority of membrane integrated amino acids are primarily non-polar/hydrophobic and adopt an α-helical conformation. These stretches are typically around 20 amino acids long and are known as transmembrane (TM) helices. In this review, we will consider how transmembrane helices achieve membrane integration. We will address questions such as: Where do the stretches of amino acids fold into a helical conformation? What is/are the route/routes that these stretches take from synthesis at the ribosome to integration through the ER translocon? How do these stretches ‘know’ to integrate and in which orientation? How do marginally hydrophobic stretches of amino acids integrate and survive as transmembrane helices?.

Original languageEnglish
Article number12778
JournalInternational Journal of Molecular Sciences
Issue number23
Early online date26 Nov 2021
Publication statusPublished - 1 Dec 2021


  • Folding
  • Insertion
  • Membrane protein
  • Ribosome
  • Translocon
  • Transmembrane segment

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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