Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Peptide Location Fingerprinting Reveals Tissue Region-specific Differences in Protein Structures in an Ageing Human Organ

Alexander Eckersley
* ORCID logo ,
Matiss Ozols
,
Peikai Chen
ORCID logo ,
Vivian Tam
,
Judith A Hoyland
,
Andrew Trafford
,
Danny Chan
ORCID logo ,
Michael J Sherratt
* ORCID logo
Version 1 : Received: 29 July 2021 / Approved: 29 July 2021 / Online: 29 July 2021 (15:46:49 CEST)

A peer-reviewed article of this Preprint also exists.

Eckersley, A.; Ozols, M.; Chen, P.; Tam, V.; Hoyland, J.A.; Trafford, A.; Chan, D.; Sherratt, M.J. Peptide Location Fingerprinting Reveals Tissue Region-Specific Differences in Protein Structures in an Ageing Human Organ. Int. J. Mol. Sci. 2021, 22, 10408. Eckersley, A.; Ozols, M.; Chen, P.; Tam, V.; Hoyland, J.A.; Trafford, A.; Chan, D.; Sherratt, M.J. Peptide Location Fingerprinting Reveals Tissue Region-Specific Differences in Protein Structures in an Ageing Human Organ. Int. J. Mol. Sci. 2021, 22, 10408.

Abstract

In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due to diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable of identifying proteins exhibiting structural differences in complex proteomes. PLF applied to published young and aged intervertebral disc (IVD) MS datasets (posterior, lateral and anterior regions of the annulus fibrosus), identified 268 proteins with age-related structural differences. For several ECM assemblies (collagens I, II and V and aggrecan), these differences were markedly conserved between degeneration-prone (posterior and lateral) and resistant (anterior) regions. Significant differences in peptide yields, observed within collagen I, II and V α-chains (COL1A2, COL2A1, COL5A1), were located within their triple helical regions and/or cleaved C-terminal propeptides, indicating potential accumulation of damage and impaired maintenance in ageing. Several proteins (COL5A1, COL2A1 and aggrecan) also exhibited tissue region (lateral)-specific differences in structure between aged and young, suggesting that some ageing mechanisms may act locally within tissues. This study not only provides evidence of age-related changes in ECM protein structures which are tissue-region specific, but also highlights the ability of PLF to identify potential protein biomarkers of localised tissue remodelling.

Keywords

proteomics; peptide location fingerprinting; extracellular matrix; biomarkers; ageing; intervertebral disc; spine; mass spectrometry

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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