2MOV

Receptor for Advanced Glycation End Products (RAGE) Specifically Recognizes Methylglyoxal Derived AGEs.

Summary for 2MOV

• Entry DOI: 10.2210/pdb2mov/pdb
• NMR Information: BMRB: 19953
• Descriptor: Advanced glycosylation end product-specific receptor, N~5~-[(5R)-5-methyl-4-oxo-4,5-dihydro-1H-imidazol-2-yl]-L-ornithine (2 entities in total)
• Functional Keywords: protein/ligand, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: Q15109
• Total number of polymer chains: 1
• Total formula weight: 11799.57

Authors

Shekhtman, A.,Xue, J.,Ray, R.,Singer, D.,Bohme, D.,Burz, D.S.,Rai, V.,Hoffman, R. (deposition date: 2014-05-05, release date: 2014-06-25, Last modification date: 2024-10-30)

Primary citation

Xue, J.,Ray, R.,Singer, D.,Bohme, D.,Burz, D.S.,Rai, V.,Hoffmann, R.,Shekhtman, A.
The Receptor for Advanced Glycation End Products (RAGE) Specifically Recognizes Methylglyoxal-Derived AGEs.
Biochemistry, 53:3327-3335, 2014

PubMed Abstract: Diabetes-induced hyperglycemia increases the extracellular concentration of methylglyoxal. Methylglyoxal-derived hydroimidazolones (MG-H) form advanced glycation end products (AGEs) that accumulate in the serum of diabetic patients. The binding of hydroimidozolones to the receptor for AGEs (RAGE) results in long-term complications of diabetes typified by vascular and neuronal injury. Here we show that binding of methylglyoxal-modified albumin to RAGE results in signal transduction. Chemically synthesized peptides containing hydroimidozolones bind specifically to the V domain of RAGE with nanomolar affinity. The solution structure of an MG-H1-V domain complex revealed that the hydroimidazolone moiety forms multiple contacts with a positively charged surface on the V domain. The high affinity and specificity of hydroimidozolones binding to the V domain of RAGE suggest that they are the primary AGE structures that give rise to AGEs-RAGE pathologies.

PubMed: 24824951
DOI: 10.1021/bi500046t

Experimental method

SOLUTION NMR