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PDBsum entry 3o3u
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Transport protein, signaling protein
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PDB id
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3o3u
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References listed in PDB file
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Key reference
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Title
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The 1.5 å crystal structure of human receptor for advanced glycation endproducts (rage) ectodomains reveals unique features determining ligand binding.
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Authors
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H.Park,
F.G.Adsit,
J.C.Boyington.
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Ref.
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J Biol Chem, 2010,
285,
40762-40770.
[DOI no: ]
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PubMed id
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Abstract
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Interaction of the pattern recognition receptor, RAGE with key ligands such as
advanced glycation end products (AGE), S100 proteins, amyloid β, and HMGB1 has
been linked to diabetic complications, inflammatory and neurodegenerative
disorders, and cancer. To help answer the question of how a single receptor can
recognize and respond to a diverse set of ligands we have investigated the
structure and binding properties of the first two extracellular domains of human
RAGE, which are implicated in various ligand binding and subsequent signaling
events. The 1.5-Å crystal structure reveals an elongated molecule with a large
basic patch and a large hydrophobic patch, both highly conserved. Isothermal
titration calorimetry (ITC) and deletion experiments indicate S100B recognition
by RAGE is an entropically driven process involving hydrophobic interaction that
is dependent on Ca(2+) and on residues in the C'D loop (residues 54-67) of
domain 1. In contrast, competition experiments using gel shift assays suggest
that RAGE interaction with AGE is driven by the recognition of negative charges
on AGE-proteins. We also demonstrate that RAGE can bind to dsDNA and dsRNA.
These findings reveal versatile structural features of RAGE that help explain
its ability to recognize of multiple ligands.
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