IIBBA 05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
artículos
Título:
5- The irreversible binding of amyloid peptide substrates to insulin-degrading enzyme. A biological perspective
Autor/es:
DE TULLIO MATIAS; MORELLI LAURA; CASTAñO EDUARDO
Revista:
Prion
Referencias:
Año: 2008 vol. 2 p. 51 - 56
Resumen:
Insulin-degrading enzyme (IDE) is a conserved Zn2+metalloendopeptidase involved in insulin degradation and in the maintenance of brain steady-state levels of amyloid â peptide (Aâ) of Alzheimers disease (AD). Our recent demonstration that IDE and Aâ are capable of forming a stoichiometric and extremely stable complex raises several intriguing possibilities regarding the role of this unique protein-peptide interaction in physiological and pathological conditions. These include a protective cellular function of IDE as a dead-end chaperone alternative to its proteolytic activity and the potential impact of the irreversible binding of Aâ to IDE upon its role as a varicella zoster virus receptor. In a pathological context, the implications for insulin signaling and its relationship to AD and novel interaction between amyloidogenic peptides and other Zn2+metallopeptidases with an IDE-like fold and a substrate conformation-dependent recognition echanism.2+metalloendopeptidase involved in insulin degradation and in the maintenance of brain steady-state levels of amyloid â peptide (Aâ) of Alzheimers disease (AD). Our recent demonstration that IDE and Aâ are capable of forming a stoichiometric and extremely stable complex raises several intriguing possibilities regarding the role of this unique protein-peptide interaction in physiological and pathological conditions. These include a protective cellular function of IDE as a dead-end chaperone alternative to its proteolytic activity and the potential impact of the irreversible binding of Aâ to IDE upon its role as a varicella zoster virus receptor. In a pathological context, the implications for insulin signaling and its relationship to AD and novel interaction between amyloidogenic peptides and other Zn2+metallopeptidases with an IDE-like fold and a substrate conformation-dependent recognition echanism.
