2L7U

Structure of CEL-PEP-RAGE V domain complex

Summary for 2L7U

• Entry DOI: 10.2210/pdb2l7u/pdb
• NMR Information: BMRB: 17378
• Descriptor: Advanced glycosylation end product-specific receptor, Serum albumin peptide (2 entities in total)
• Functional Keywords: v domain, allergen, cleavage on pair of basic residues, lipid-binding, metal-binding, phosphoprotein, secreted
• Biological source: Homo sapiens (human); More
• Cellular location: Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted. Isoform 10: Cell membrane ; Single-pass type I membrane protein : Q15109; Secreted: P02769
• Total number of polymer chains: 2
• Total formula weight: 12494.21

Authors

Xue, J.,Rai, V.,Schmidt, A.,Frolov, S.,Reverdatto, S.,Singer, D.,Chabierski, S.,Xie, J.,Burz, D.,Shekhtman, A.,Hoffman, R. (deposition date: 2010-12-23, release date: 2011-05-18, Last modification date: 2023-11-29)

Primary citation

Xue, J.,Rai, V.,Singer, D.,Chabierski, S.,Xie, J.,Reverdatto, S.,Burz, D.S.,Schmidt, A.M.,Hoffmann, R.,Shekhtman, A.
Advanced glycation end product recognition by the receptor for AGEs.
Structure, 19:722-732, 2011

PubMed Abstract: Nonenzymatic protein glycation results in the formation of advanced glycation end products (AGEs) that are implicated in the pathology of diabetes, chronic inflammation, Alzheimer's disease, and cancer. AGEs mediate their effects primarily through a receptor-dependent pathway in which AGEs bind to a specific cell surface associated receptor, the Receptor for AGEs (RAGE). N(ɛ)-carboxy-methyl-lysine (CML) and N(ɛ)-carboxy-ethyl-lysine (CEL), constitute two of the major AGE structures found in tissue and blood plasma, and are physiological ligands of RAGE. The solution structure of a CEL-containing peptide-RAGE V domain complex reveals that the carboxyethyl moiety fits inside a positively charged cavity of the V domain. Peptide backbone atoms make specific contacts with the V domain. The geometry of the bound CEL peptide is compatible with many CML (CEL)-modified sites found in plasma proteins. The structure explains how such patterned ligands as CML (CEL)-proteins bind to RAGE and contribute to RAGE signaling.

PubMed: 21565706
DOI: 10.1016/j.str.2011.02.013

Experimental method

SOLUTION NMR