Molecular signatures of long‐lived proteins: autolytic cleavage adjacent to serine residues

Aging Cell

Shih-Ping Su¹  Brian Lyons³  Michael Friedrich³  Jason D. McArthur¹  Xiaomin Song²  Dylan Xavier²  Roger J. W. Truscott¹ 

[1]Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia

[2]Australian Proteome Analysis Facility, Level 4, Building F7B, Research Park Drive, Macquarie University, Sydney, NSW 2109, Australia

[3]Save Sight Institute, Sydney University, 8 Macquarie St, Sydney, NSW 2000, Australia

关键词: human lens;    long‐lived proteins;    protein instability;    proteolysis;    spontaneous cleavage;   

DOI  :  10.1111/j.1474-9726.2012.00860.x

来源: Wiley

【 摘 要 】

Summary

The centre of the human lens, which is composed of proteins that were synthesized prior to birth, is an ideal model for the evaluation of long-term protein stability and processes responsible for the degradation of macromolecules. By analysing the sequences of peptides present in human lens nuclei, characteristic features of intrinsic protein instability were determined. Prominent was the cleavage on the N-terminal side of serine residues. Despite accounting for just 9% of the amino acid composition of crystallins, peptides with N-terminal Ser represented one-quarter of all peptides. Nonenzymatic cleavage at Ser could be reproduced by incubating peptides at elevated temperatures. Serine residues may thus represent susceptible sites for autolysis in polypeptides exposed to physiological conditions over a period of years. Once these sites are cleaved, other chemical processes result in progressive removal or ‘laddering’ of amino acid residues from newly exposed N- and C-termini. As N-terminal Ser peptides originated from several crystallins with unrelated sequences, this may represent a general feature of long-lived proteins.

【 授权许可】

Unknown   
© 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland