Peptide location fingerprinting reveals modification-associated biomarker candidates of ageing in human tissue proteomes.
Aging Cell
; 20(5): e13355, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33830638
ABSTRACT
Although dysfunctional protein homeostasis (proteostasis) is a key factor in many age-related diseases, the untargeted identification of structurally modified proteins remains challenging. Peptide location fingerprinting is a proteomic analysis technique capable of identifying structural modification-associated differences in mass spectrometry (MS) data sets of complex biological samples. A new webtool (Manchester Peptide Location Fingerprinter), applied to photoaged and intrinsically aged skin proteomes, can relatively quantify peptides and map statistically significant differences to regions within protein structures. New photoageing biomarker candidates were identified in multiple pathways including extracellular matrix organisation (collagens and proteoglycans), protein synthesis and folding (ribosomal proteins and TRiC complex subunits), cornification (keratins) and hemidesmosome assembly (plectin and integrin α6ß4). Crucially, peptide location fingerprinting uniquely identified 120 protein biomarker candidates in the dermis and 71 in the epidermis which were modified as a consequence of photoageing but did not differ significantly in relative abundance (measured by MS1 ion intensity). By applying peptide location fingerprinting to published MS data sets, (identifying biomarker candidates including collagen V and versican in ageing tendon) we demonstrate the potential of the MPLF webtool for biomarker discovery.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pele
/
Mapeamento de Peptídeos
/
Envelhecimento da Pele
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Proteômica
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
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Humans
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Middle aged
Idioma:
En
Revista:
Aging Cell
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido