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

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• 作者：Jing Xue ; Rashmi Ray ; David Singer ; David B枚hme ; David S. Burz ; Vivek Rai ; Ralf Hoffmann ; Alexander Shekhtman
• 刊名：Biochemistry
• 出版年：2014
• 出版时间：May 27, 2014
• 年：2014
• 卷：53
• 期：20
• 页码：3327-3335
• 全文大小：459K
• 年卷期：v.53,no.20(May 27, 2014)
• ISSN：1520-4995

文摘

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鈥揤 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鈥揜AGE pathologies.