Unknown

Dataset Information

0

The irreversible binding of amyloid peptide substrates to insulin-degrading enzyme: a biological perspective.


ABSTRACT: Insulin-degrading enzyme (IDE) is a conserved Zn(2+)metalloendopeptidase involved in insulin degradation and in the maintenance of brain steady-state levels of amyloid beta peptide (Abeta) of Alzheimer's disease (AD). Our recent demonstration that IDE and Abeta 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 Abeta 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 pathogenesis are discussed. Moreover, our findings warrant further research regarding a possible general and novel interaction between amyloidogenic peptides and other Zn(2+)metallopeptidases with an IDE-like fold and a substrate conformation-dependent recognition mechanism.

SUBMITTER: de Tullio MB 

PROVIDER: S-EPMC2634517 | biostudies-literature | 2008 Apr-Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

The irreversible binding of amyloid peptide substrates to insulin-degrading enzyme: a biological perspective.

de Tullio Matías B MB   Morelli Laura L   Castaño Eduardo M EM  

Prion 20080401 2


Insulin-degrading enzyme (IDE) is a conserved Zn(2+)metalloendopeptidase involved in insulin degradation and in the maintenance of brain steady-state levels of amyloid beta peptide (Abeta) of Alzheimer's disease (AD). Our recent demonstration that IDE and Abeta 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 prote  ...[more]

Similar Datasets

| S-EPMC3623905 | biostudies-literature
| S-EPMC2756532 | biostudies-literature
| S-EPMC3642335 | biostudies-literature
| S-EPMC2652632 | biostudies-literature
| S-EPMC3039328 | biostudies-literature
| S-EPMC8169600 | biostudies-literature
| S-EPMC6633413 | biostudies-literature
| S-EPMC153065 | biostudies-literature
| S-EPMC7830943 | biostudies-literature
| S-EPMC6188057 | biostudies-literature