Exploring the unmapped cysteine redox proteoform landscape.
Am J Physiol Cell Physiol
; 2024 Aug 05.
Article
in En
| MEDLINE
| ID: mdl-39099422
ABSTRACT
Cysteine redox proteoforms define the diverse molecular states that proteins with cysteine residues can adopt. A protein with one cysteine residue must adopt one of two binary proteoforms reduced or oxidised. Their numbers scale A protein with ten cysteine residues must assume one of 1,024 proteoforms. Although they play pivotal biological roles, the vast cysteine redox proteoform landscape comprising vast numbers of theoretical proteoforms remains largely uncharted. Progress is hampered by a general underappreciation of cysteine redox proteoforms, their intricate complexity, and the formidable challenges that they pose to existing methods. The present review advances cysteine redox proteoform theory, scrutinises methodological barriers, and elaborates innovative technologies for detecting unique residue-defined cysteine redox proteoforms. For example, chemistry-enabled hybrid approaches combining the strengths of top-down and bottom-up mass spectrometry for systematically cataloguing cysteine redox proteoforms are delineated. These methods provide the technological means to map uncharted redox terrain. To unravel hidden redox regulatory mechanisms, discover new biomarkers, and pinpoint therapeutic targets by mining the theoretical cysteine redox proteoform space, a community-wide initiative termed the 'Human Cysteine Redox Proteoform Project' is proposed. Exploring the cysteine redox proteoform landscape could transform current understanding of redox biology.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Am J Physiol Cell Physiol
Journal subject:
FISIOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
United kingdom