PMID- 23374350
OWN - NLM
STAT- MEDLINE
DCOM- 20130328
LR  - 20230425
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 152
IP  - 3
DP  - 2013 Jan 31
TI  - Architecture and membrane interactions of the EGF receptor.
PG  - 557-69
LID - S0092-8674(12)01552-8 [pii]
LID - 10.1016/j.cell.2012.12.030 [doi]
AB  - Dimerization-driven activation of the intracellular kinase domains of the 
      epidermal growth factor receptor (EGFR) upon extracellular ligand binding is 
      crucial to cellular pathways regulating proliferation, migration, and 
      differentiation. Inactive EGFR can exist as both monomers and dimers, suggesting 
      that the mechanism regulating EGFR activity may be subtle. The membrane itself 
      may play a role but creates substantial difficulties for structural studies. Our 
      molecular dynamics simulations of membrane-embedded EGFR suggest that, in 
      ligand-bound dimers, the extracellular domains assume conformations favoring 
      dimerization of the transmembrane helices near their N termini, dimerization of 
      the juxtamembrane segments, and formation of asymmetric (active) kinase dimers. 
      In ligand-free dimers, by holding apart the N termini of the transmembrane 
      helices, the extracellular domains instead favor C-terminal dimerization of the 
      transmembrane helices, juxtamembrane segment dissociation and membrane burial, 
      and formation of symmetric (inactive) kinase dimers. Electrostatic interactions 
      of EGFR's intracellular module with the membrane are critical in maintaining this 
      coupling.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Arkhipov, Anton
AU  - Arkhipov A
AD  - D. E. Shaw Research, New York, NY 10036, USA.
FAU - Shan, Yibing
AU  - Shan Y
FAU - Das, Rahul
AU  - Das R
FAU - Endres, Nicholas F
AU  - Endres NF
FAU - Eastwood, Michael P
AU  - Eastwood MP
FAU - Wemmer, David E
AU  - Wemmer DE
FAU - Kuriyan, John
AU  - Kuriyan J
FAU - Shaw, David E
AU  - Shaw DE
LA  - eng
GR  - HHMI_/Howard Hughes Medical Institute/United States
GR  - R01 CA096504/CA/NCI NIH HHS/United States
GR  - 2-R01-CA096504-06/CA/NCI NIH HHS/United States
GR  - CAPMC/CIHR/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Membrane Lipids)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Cell Membrane/chemistry/*metabolism
MH  - Dimerization
MH  - ErbB Receptors/*chemistry/metabolism
MH  - Humans
MH  - Membrane Lipids/metabolism
MH  - Molecular Dynamics Simulation
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Protein Conformation
MH  - Protein Structure, Tertiary
MH  - Static Electricity
PMC - PMC3680629
MID - NIHMS459031
OID - NLM: HHMIMS459031
EDAT- 2013/02/05 06:00
MHDA- 2013/03/30 06:00
PMCR- 2013/07/31
CRDT- 2013/02/05 06:00
PHST- 2012/07/10 00:00 [received]
PHST- 2012/09/28 00:00 [revised]
PHST- 2012/12/10 00:00 [accepted]
PHST- 2013/02/05 06:00 [entrez]
PHST- 2013/02/05 06:00 [pubmed]
PHST- 2013/03/30 06:00 [medline]
PHST- 2013/07/31 00:00 [pmc-release]
AID - S0092-8674(12)01552-8 [pii]
AID - 10.1016/j.cell.2012.12.030 [doi]
PST - ppublish
SO  - Cell. 2013 Jan 31;152(3):557-69. doi: 10.1016/j.cell.2012.12.030.