PMID- 21822280
OWN - NLM
STAT- MEDLINE
DCOM- 20111108
LR  - 20211020
IS  - 1545-9985 (Electronic)
IS  - 1545-9993 (Print)
IS  - 1545-9985 (Linking)
VI  - 18
IP  - 9
DP  - 2011 Aug 7
TI  - Simultaneous visualization of the extracellular and cytoplasmic domains of the 
      epidermal growth factor receptor.
PG  - 984-9
LID - 10.1038/nsmb.2092 [doi]
AB  - To our knowledge, no structural study to date has characterized, in an intact 
      receptor, the coupling of conformational change in extracellular domains through 
      a single-pass transmembrane domain to conformational change in cytoplasmic 
      domains. Here we examine such coupling, and its unexpected complexity, using 
      nearly full-length epidermal growth factor receptor (EGFR) and negative-stain EM. 
      The liganded, dimeric EGFR ectodomain can couple both to putatively active, 
      asymmetrically associated kinase dimers and to putatively inactive, symmetrically 
      associated kinase dimers and monomers. Inhibitors that stabilize the active or 
      inactive conformation of the kinase active site, as well as mutations in the 
      kinase dimer interface and a juxtamembrane phosphorylation site, shift the 
      equilibrium among the three kinase association states. This coupling of one 
      conformation of an activated receptor ectodomain to multiple kinase-domain 
      arrangements reveals previously unanticipated complexity in transmembrane 
      signaling and facilitates regulation of receptor function in the juxtamembrane 
      and cytoplasmic environments.
FAU - Mi, Li-Zhi
AU  - Mi LZ
AD  - Immune Disease Institute and Department of Pathology, Harvard Medical School, 
      Boston, Massachusetts, USA.
FAU - Lu, Chafen
AU  - Lu C
FAU - Li, Zongli
AU  - Li Z
FAU - Nishida, Noritaka
AU  - Nishida N
FAU - Walz, Thomas
AU  - Walz T
FAU - Springer, Timothy A
AU  - Springer TA
LA  - eng
GR  - P01 HL048675/HL/NHLBI NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - HL-48675/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110807
PL  - United States
TA  - Nat Struct Mol Biol
JT  - Nature structural & molecular biology
JID - 101186374
RN  - 0 (Ligands)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
CIN - Nat Struct Mol Biol. 2012 Jan;19(1):1-3. PMID: 22218287
MH  - Catalytic Domain
MH  - Dimerization
MH  - ErbB Receptors/*chemistry/genetics/ultrastructure
MH  - Humans
MH  - Ligands
MH  - Mutation
MH  - Protein Structure, Tertiary
PMC - PMC4117315
MID - NIHMS609904
EDAT- 2011/08/09 06:00
MHDA- 2011/11/09 06:00
PMCR- 2014/07/31
CRDT- 2011/08/09 06:00
PHST- 2011/02/02 00:00 [received]
PHST- 2011/05/25 00:00 [accepted]
PHST- 2011/08/09 06:00 [entrez]
PHST- 2011/08/09 06:00 [pubmed]
PHST- 2011/11/09 06:00 [medline]
PHST- 2014/07/31 00:00 [pmc-release]
AID - nsmb.2092 [pii]
AID - 10.1038/nsmb.2092 [doi]
PST - epublish
SO  - Nat Struct Mol Biol. 2011 Aug 7;18(9):984-9. doi: 10.1038/nsmb.2092.