Oxiforms: Unique cysteine residue‐ and chemotype‐specified chemical combinations can produce functionally‐distinct proteoforms. Like how mixing primary colours creates new shades, cysteine residue- and chemotype-specified chemical combinations can produce functionally-distinct proteoforms called oxiforms

TY - JOUR

T1 - Oxiforms

T2 - Unique cysteine residue‐ and chemotype‐specified chemical combinations can produce functionally‐distinct proteoforms. Like how mixing primary colours creates new shades, cysteine residue- and chemotype-specified chemical combinations can produce functionally-distinct proteoforms called oxiforms

AU - Cobley, James N.

N1 - Copyright © 2023 The Authors. BioEssays published by Wiley Periodicals LLC.

PY - 2023/7

Y1 - 2023/7

N2 - A single protein molecule with one or more cysteine residues can occupy a plurality of unique residue and oxidation-chemotype specified proteoforms that I term oxiforms. In binary reduced or oxidised terms, one molecule with three cysteines will adopt one of eight unique oxiforms. Residue-defined sulfur chemistry endows specific oxiforms with distinct functionally-relevant biophysical properties (e.g., steric effects). Their emergent complexity means a functionally-relevant effect may only manifest when multiple cysteines are oxidised. Like how mixing colours makes new shades, combining discrete redox chemistries—colours—can create a kaleidoscope of oxiform hues. The sheer diversity of oxiforms co-existing within the human body provides a biological basis for redox heterogeneity. Of evolutionary significance, oxiforms may enable individual cells to mount a broad spectrum of responses to the same stimulus. Their biological significance, however plausible, is speculative because protein-specific oxiforms remain essentially unexplored. Excitingly, pioneering new techniques can push the field into uncharted territory by quantifying oxiforms. The oxiform concept can advance our understanding of redox-regulation in health and disease.

AB - A single protein molecule with one or more cysteine residues can occupy a plurality of unique residue and oxidation-chemotype specified proteoforms that I term oxiforms. In binary reduced or oxidised terms, one molecule with three cysteines will adopt one of eight unique oxiforms. Residue-defined sulfur chemistry endows specific oxiforms with distinct functionally-relevant biophysical properties (e.g., steric effects). Their emergent complexity means a functionally-relevant effect may only manifest when multiple cysteines are oxidised. Like how mixing colours makes new shades, combining discrete redox chemistries—colours—can create a kaleidoscope of oxiform hues. The sheer diversity of oxiforms co-existing within the human body provides a biological basis for redox heterogeneity. Of evolutionary significance, oxiforms may enable individual cells to mount a broad spectrum of responses to the same stimulus. Their biological significance, however plausible, is speculative because protein-specific oxiforms remain essentially unexplored. Excitingly, pioneering new techniques can push the field into uncharted territory by quantifying oxiforms. The oxiform concept can advance our understanding of redox-regulation in health and disease.

KW - chemotype

KW - cysteine

KW - oxiforms

KW - proteoform

KW - redox

UR - https://www.scopus.com/pages/publications/85158142574

U2 - 10.1002/bies.202200248

DO - 10.1002/bies.202200248

M3 - Article

C2 - 37147790

SN - 0265-9247

VL - 45

JO - BioEssays

JF - BioEssays

IS - 7

M1 - 2200248

ER -