PMID- 17121827
OWN - NLM
STAT- MEDLINE
DCOM- 20070307
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 2
DP  - 2007 Jan 12
TI  - Specific high affinity interactions of monomeric endotoxin.protein complexes with 
      Toll-like receptor 4 ectodomain.
PG  - 1010-7
AB  - Potent Toll-like receptor 4 (TLR4) activation by endotoxin has been intensely 
      studied, but the molecular requirements for endotoxin interaction with TLR4 are 
      still incompletely defined. Ligand-receptor interactions involving endotoxin and 
      TLR4 were characterized using monomeric endotoxin.protein complexes of high 
      specific radioactivity. The binding of endotoxin.MD-2 to the TLR4 ectodomain 
      (TLR4ECD) and transfer of endotoxin from CD14 to MD-2/TLR4ECD were demonstrated 
      using HEK293T-conditioned medium containing TLR4ECD+/-MD-2. These interactions 
      are specific, of high affinity (KD<300 pm), and consistent with the molecular 
      requirements for potent cell activation by endotoxin. Both reactions result in 
      the formation of a Mr approximately 190,000 complex composed of endotoxin, MD-2, 
      and TLR4ECD. CD14 facilitates transfer of endotoxin to MD-2 (TLR4) but is not a 
      stable component of the endotoxin.MD-2/TLR4 complex. The ability to assay 
      specific high affinity interactions of monomeric endotoxin.protein complexes with 
      TLR4ECD should allow better definition of the structural requirements for 
      endotoxin-induced TLR4 activation.
FAU - Prohinar, Polonca
AU  - Prohinar P
AD  - Inflammation Program, Department of Internal Medicine, Roy J. and Lucille A. 
      Carver College of Medicine, University of Iowa, and Veterans Affairs Medical 
      Center, Iowa City, Iowa 52242, USA.
FAU - Re, Fabio
AU  - Re F
FAU - Widstrom, Richard
AU  - Widstrom R
FAU - Zhang, DeSheng
AU  - Zhang D
FAU - Teghanemt, Athmane
AU  - Teghanemt A
FAU - Weiss, Jerrold P
AU  - Weiss JP
FAU - Gioannini, Theresa L
AU  - Gioannini TL
LA  - eng
GR  - AI59372/AI/NIAID NIH HHS/United States
GR  - P0144642/PHS HHS/United States
GR  - R21 AI54665/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20061122
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Endotoxins)
RN  - 0 (Ligands)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Lymphocyte Antigen 96)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 10028-17-8 (Tritium)
SB  - IM
MH  - Acylation
MH  - Cell Line
MH  - Endotoxins/*metabolism
MH  - Humans
MH  - Kidney/cytology
MH  - Ligands
MH  - Lipopolysaccharide Receptors/metabolism
MH  - Lymphocyte Antigen 96/metabolism
MH  - Protein Binding/physiology
MH  - Protein Structure, Tertiary
MH  - Solubility
MH  - Toll-Like Receptor 4/*chemistry/*metabolism
MH  - Tritium
EDAT- 2006/11/24 09:00
MHDA- 2007/03/08 09:00
CRDT- 2006/11/24 09:00
PHST- 2006/11/24 09:00 [pubmed]
PHST- 2007/03/08 09:00 [medline]
PHST- 2006/11/24 09:00 [entrez]
AID - S0021-9258(20)73527-1 [pii]
AID - 10.1074/jbc.M609400200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Jan 12;282(2):1010-7. doi: 10.1074/jbc.M609400200. Epub 2006 
      Nov 22.