PDBsum entry 3o3u

Transport protein, signaling protein

PDB id: 3o3u

Contents

Protein chain

580 a.a. *

Ligands

GLC-GLC-GLC

SO4

Waters ×985

* Residue conservation analysis

PDB id:

3o3u

Name:

Transport protein, signaling protein

Title:

Crystal structure of human receptor for advanced glycation endproducts (rage)

Structure:

Maltose-binding periplasmic protein, advanced glycosylation end product-specific receptor. Chain: n. Fragment: mbp: unp residues 28-384, rage: unp residues 23-231. Synonym: mmbp, maltodextrin-binding protein. Engineered: yes

Source:

Escherichia coli, homo sapiens. Organism_taxid: 562, 9606. Gene: b4034, jw3994, male, rage, ager. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.50Å R-factor: 0.169 R-free: 0.184

Authors:

H.Park,J.C.Boyington

Key ref:

H.Park et al. (2010). The 1.5 Å crystal structure of human receptor for advanced glycation endproducts (RAGE) ectodomains reveals unique features determining ligand binding. J Biol Chem, 285, 40762-40770. PubMed id: 20943659 DOI: 10.1074/jbc.M110.169276

Date:

26-Jul-10 Release date: 13-Oct-10

Protein chain

P0AEX9  (MALE_ECOLI) -  Maltose/maltodextrin-binding periplasmic protein from Escherichia coli (strain K12)

Seq: 396 a.a.

Struc: 580 a.a.*

Protein chain

Q15109  (RAGE_HUMAN) -  Advanced glycosylation end product-specific receptor from Homo sapiens

Seq: 404 a.a.

Struc: 580 a.a.*

* PDB and UniProt seqs differ at 26 residue positions (black crosses)

DOI no: 10.1074/jbc.M110.169276

J Biol Chem 285:40762-40770 (2010)

PubMed id: 20943659

The 1.5 Å crystal structure of human receptor for advanced glycation endproducts (RAGE) ectodomains reveals unique features determining ligand binding.

H.Park, F.G.Adsit, J.C.Boyington.

ABSTRACT

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.