Issue 1, 2016

Copper binding to naturally occurring, lactam form of angiogenin differs from that to recombinant protein, affecting their activity

Abstract

Angiogenin is a member of the ribonuclease family and a normal constituent of human plasma. It is one of the most potent angiogenic factors known and is overexpressed in different types of cancers. Copper is also an essential cofactor in angiogenesis and, during this process, it is mobilized from inside to outside of the cell. To date, contrasting results have been reported about copper(II) influencing angiogenin activity. However, in these studies, the recombinant form of the protein was used. Unlike recombinant angiogenin, that contains an extra methionine with a free terminal amino group, the naturally occurring protein present in human plasma starts with a glutamine residue that spontaneously cyclizes to pyroglutamate, a lactam derivative. Herein, we report spectroscopic evidence indicating that copper(II) experiences different coordination environments in the two protein isoforms, and affects their RNase and angiogenic activity differently. These results show how relatively small differences between recombinant and wild type proteins can result in markedly different behaviours.

Graphical abstract: Copper binding to naturally occurring, lactam form of angiogenin differs from that to recombinant protein, affecting their activity

Supplementary files

Article information

Article type
Paper
Submitted
10 Aug 2015
Accepted
12 Nov 2015
First published
12 Nov 2015

Metallomics, 2016,8, 118-124

Author version available

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