TY - JOUR
T1 - Oxiforms
T2 - Unique cysteine residue- and chemotype-specified chemical combinations can produce functionally-distinct proteoforms
AU - Cobley, James N
N1 - © 2023 The Authors. BioEssays published by Wiley Periodicals LLC.
PY - 2023/5/5
Y1 - 2023/5/5
N2 - Like how mixing primary colours creates new shades, cysteine residue- and chemotype-specified chemical combinations can produce functionally-distinct proteoforms called oxiformsA 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 - Like how mixing primary colours creates new shades, cysteine residue- and chemotype-specified chemical combinations can produce functionally-distinct proteoforms called oxiformsA 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.
U2 - 10.1002/bies.202200248
DO - 10.1002/bies.202200248
M3 - Article
C2 - 37147790
SN - 0265-9247
VL - 45
SP - e2200248
JO - BioEssays : news and reviews in molecular, cellular and developmental biology
JF - BioEssays : news and reviews in molecular, cellular and developmental biology
IS - 7
ER -