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Structural Basis for Ligand Recognition and Activation of RAGE
- Source :
- Structure. 18(10):1342-1352
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- SummaryThe receptor for advanced glycation end products (RAGE) is a pattern recognition receptor involved in inflammatory processes and is associated with diabetic complications, tumor outgrowth, and neurodegenerative disorders. RAGE induces cellular signaling events upon binding of a variety of ligands, such as glycated proteins, amyloid-β, HMGB1, and S100 proteins. The X-ray crystal structure of the VC1 ligand-binding region of the human RAGE ectodomain was determined at 1.85 Å resolution. The VC1 ligand-binding surface was mapped onto the structure from titrations with S100B monitored by heteronuclear NMR spectroscopy. These NMR chemical shift perturbations were used as input for restrained docking calculations to generate a model for the VC1-S100B complex. Together, the arrangement of VC1 molecules in the crystal and complementary biochemical studies suggest a role for self-association in RAGE function. Our results enhance understanding of the functional outcomes of S100 protein binding to RAGE and provide insight into mechanistic models for how the receptor is activated.
- Subjects :
- Models, Molecular
Protein Folding
Magnetic Resonance Spectroscopy
Molecular Sequence Data
Receptor for Advanced Glycation End Products
S100 Calcium Binding Protein beta Subunit
Plasma protein binding
Crystallography, X-Ray
Ligands
HMGB1
Article
Protein Structure, Secondary
03 medical and health sciences
0302 clinical medicine
Structural Biology
Animals
Humans
Amino Acid Sequence
Nerve Growth Factors
Receptors, Immunologic
Binding site
Receptor
Molecular Biology
030304 developmental biology
0303 health sciences
Binding Sites
Sequence Homology, Amino Acid
biology
Chemistry
S100 Proteins
Hydrogen-Ion Concentration
S100 protein binding
Protein Structure, Tertiary
Kinetics
Biochemistry
Ectodomain
Docking (molecular)
biology.protein
Biophysics
Protein folding
030217 neurology & neurosurgery
Protein Binding
Subjects
Details
- ISSN :
- 09692126
- Volume :
- 18
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Structure
- Accession number :
- edsair.doi.dedup.....4b5b3a2aff36ee77e585d46b6c0b33ce
- Full Text :
- https://doi.org/10.1016/j.str.2010.05.017