N-Glycosylation as determinant of epidermal growth factor receptor conformation in membranes

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

The epidermal growth factor receptor (EGFR) regulates several critical cellular processes and is an important target for cancer therapy. In lieu of a crystallographic structure of the complete receptor, atomistic molecular dynamics (MD) simulations have recently shown that they can excel in studies of the full-length receptor. Here we present atomistic MD simulations of the monomeric N-glycosylated human EGFR in biomimetic lipid bilayers that are, in parallel, also used for the reconstitution of full-length receptors. This combination enabled us to experimentally validate our simulations, using ligand binding assays and antibodies to monitor the conformational properties of the receptor reconstituted into membranes. We find that N-glycosylation is a critical determinant of EGFR conformation, and specifically the orientation of the EGFR ectodomain relative to the membrane. In the absence of a structure for full-length, posttranslationally modified membrane receptors, our approach offers new means to structurally define and experimentally validate functional properties of cell surface receptors in biomimetic membrane environments.

Details

Original languageEnglish
Pages (from-to)4334-4339
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America : PNAS
Volume112
Issue number14
Publication statusPublished - 7 Apr 2015
Peer-reviewedYes

External IDs

PubMed 25805821
ORCID /0000-0003-4375-3144/work/142255280
ORCID /0000-0003-2083-0506/work/148607264

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • EGFR, Lipid-protein interaction, Lipids, MD simulation, Proteoliposomes

Library keywords