Deep Profiling of Plasma Proteoforms with Engineered Nanoparticles for Top-Down Proteomics.
J Proteome Res
; 23(10): 4694-4703, 2024 Oct 04.
Article
em En
| MEDLINE
| ID: mdl-39312774
ABSTRACT
The dynamic range challenge for the detection of proteins and their proteoforms in human plasma has been well documented. Here, we use the nanoparticle protein corona approach to enrich low-abundance proteins selectively and reproducibly from human plasma and use top-down proteomics to quantify differential enrichment for the 2841 detected proteoforms from 114 proteins. Furthermore, nanoparticle enrichment allowed top-down detection of proteoforms between â¼1 µg/mL and â¼10 pg/mL in absolute abundance, providing up to a 105-fold increase in proteome depth over neat plasma in which only proteoforms from abundant proteins (>1 µg/mL) were detected. The ability to monitor medium and some low-abundant proteoforms through reproducible enrichment significantly extends the applicability of proteoform research by adding depth beyond albumin, immunoglobins, and apolipoproteins to uncover many involved in immunity and cell signaling. As proteoforms carry unique information content relative to peptides, this report opens the door to deeper proteoform sequencing in clinical proteomics of disease or aging cohorts.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Sanguíneas
/
Proteômica
/
Nanopartículas
Limite:
Humans
Idioma:
En
Revista:
J Proteome Res
/
J. proteome res
/
Journal of proteome research
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Estados Unidos