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Kaszuba, K.* ; Grzybek, M. ; Orłowski, A.* ; Danne, R.* ; Róg, T.* ; Simons, K.* ; Coskun, Ü. ; Vattulainen, I.*

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

Proc. Natl. Acad. Sci. U.S.A. 112, 4334–4339 (2015)
Verlagsversion DOI
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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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Egfr ; Md Simulation ; Lipids ; Lipid–protein Interaction ; Proteoliposomes; Egf-receptor; Extracellular Domain; Transmembrane Domains; Juxtamembrane Domain; Imaging Microscopy; Crystal-structure; Self-association; Structural Basis; Model Membranes; Factor-alpha
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Quellenangaben Band: 112, Heft: 14, Seiten: 4334–4339 Artikelnummer: , Supplement: ,
Verlag National Academy of Sciences
Verlagsort Washington
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)