Question

Question: Experiments in mice suggest that pyro glutamylation (see Problem 19 ) increases the rate of aggregation of $\mathbf{amyloid}\mathbf{-}\mathbf{\beta }$protein. Propose an explanation for this observation.

Short answer

Pyro glutamylation promotes self-aggregation of pyro glutamylated $\mathrm{A\beta }$ and co-aggregation of non-modified $\mathrm{A\beta }$ .

Step-by-step solution

Concept Introduction

The free amino group of glutamic acid or glutamine cycles to form a lactam in pyroglutamic acid (PCA,5-oxyproline, pidolic acid), a naturally occurring derivative of amino acids.

Increase the rate of Aggregation of  amyloid-β

Pyro glutamination of Glu drives misfolding of Ainto toxic aggregates and produces bulky hydrophobic nature to the N-terminus that might explain its enhanced aggregation properties.

Therefore, self-aggregation of pyro glutamylated A and co-aggregation of non-modified A is the result obtained.