Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2016 Sep 20;113(38):10559-64. doi: 10.1073/pnas.1606776113. Epub 2016 Sep 6.

Energetics of side-chain snorkeling in transmembrane helices probed by nonproteinogenic amino acids.

Author information

1
Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91 Stockholm, Sweden;
2
Department of Chemistry, Graduate School of Science, University of Tokyo, 113-0033 Tokyo, Japan;
3
Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91 Stockholm, Sweden; Science for Life Laboratory, Stockholm University, SE-171 21 Solna, Sweden.
4
Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91 Stockholm, Sweden; Science for Life Laboratory, Stockholm University, SE-171 21 Solna, Sweden gunnar@dbb.su.se.

Abstract

Cotranslational translocon-mediated insertion of membrane proteins into the endoplasmic reticulum is a key process in membrane protein biogenesis. Although the mechanism is understood in outline, quantitative data on the energetics of the process is scarce. Here, we have measured the effect on membrane integration efficiency of nonproteinogenic analogs of the positively charged amino acids arginine and lysine incorporated into model transmembrane segments. We provide estimates of the influence on the apparent free energy of membrane integration (ΔGapp) of "snorkeling" of charged amino acids toward the lipid-water interface, and of charge neutralization. We further determine the effect of fluorine atoms and backbone hydrogen bonds (H-bonds) on ΔGapp These results help establish a quantitative basis for our understanding of membrane protein assembly in eukaryotic cells.

KEYWORDS:

membrane protein; nonproteinogenic amino acids; translocon

PMID:
27601675
PMCID:
PMC5035864
DOI:
10.1073/pnas.1606776113
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center