Spontaneous transmembrane helix insertion thermodynamically mimics translocon-guided insertion.

Ulmschneider MB, Ulmschneider JP, Schiller N, Wallace BA, von Heijne G, White SH

Nat Commun 5 (-) 4863 [2014-09-10; online 2014-09-10]

The favourable transfer free energy for a transmembrane (TM) α-helix between the aqueous phase and lipid bilayer underlies the stability of membrane proteins. However, the connection between the energetics and process of membrane protein assembly by the Sec61/SecY translocon complex in vivo is not clear. Here, we directly determine the partitioning free energies of a family of designed peptides using three independent approaches: an experimental microsomal Sec61 translocon assay, a biophysical (spectroscopic) characterization of peptide insertion into hydrated planar lipid bilayer arrays, and an unbiased atomic-detail equilibrium folding-partitioning molecular dynamics simulation. Remarkably, the measured free energies of insertion are quantitatively similar for all three approaches. The molecular dynamics simulations show that TM helix insertion involves equilibrium with the membrane interface, suggesting that the interface may play a role in translocon-guided insertion.

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PubMed 25204588

DOI 10.1038/ncomms5863

Crossref 10.1038/ncomms5863


pmc PMC4161982

mid NIHMS617865