When absence becomes functional: lysine deserts in protein regulation and evolution.
- 1Laboratory of Protein Metabolism, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland.
Abstract
Lysine deserts-extended, continuous protein regions containing no lysine residues-occur across diverse proteomes, yet their definition, evolutionary origins and biological significance remain incompletely understood. In this Review, I examine the evidence linking local lysine depletion to protein regulation, with particular emphasis on ubiquitin- and proteasome-dependent pathways. Studies of toxin catalytic subunits and endogenous components of the ubiquitin-proteasome system show that introducing lysines at selected positions can alter ubiquitylation, protein turnover or function. These findings support a context-dependent model in which lysine deserts can limit the availability of ubiquitin acceptor sites within particular structural and enzymatic environments, rather than generally protecting entire proteins from modification or degradation. I discuss how lysine position, solvent accessibility, E3 ligase geometry and protein conformation determine the consequences of lysine introduction, and how N-terminal or non-lysine ubiquitylation as well as ubiquitin-independent proteolysis can bypass lysine depletion. I also consider the reported enrichment of lysine deserts in selected Actinobacteria and Mycobacterium phages, highlighting a testable Pup-proteasome adaptation hypothesis. Finally, I discuss potential functions beyond ubiquitylation and the methodological challenges of distinguishing selected lysine depletion from compositional bias or chance.
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BibTeX
@article{szulc2026when,
title = {{When absence becomes functional: lysine deserts in protein regulation and evolution.}},
author = {Natalia A Szulc},
journal = {Frontiers in molecular biosciences},
year = {2026},
month = oct,
doi = {10.3389/fmolb.2026.1959694},
url = {https://europepmc.org/article/MED/42928854},
note = {CC BY},
}
RIS
TY - JOUR
TI - When absence becomes functional: lysine deserts in protein regulation and evolution.
AU - Natalia A Szulc
PY - 2026
DA - 2026/10/12
JO - Frontiers in molecular biosciences
DO - 10.3389/fmolb.2026.1959694
UR - https://europepmc.org/article/MED/42928854
AB - Lysine deserts-extended, continuous protein regions containing no lysine residues-occur across diverse proteomes, yet their definition, evolutionary origins and biological significance remain incompletely understood. In this Review, I examine the evidence linking local lysine depletion to protein regulation, with particular emphasis on ubiquitin- and proteasome-dependent pathways. Studies of toxin catalytic subunits and endogenous components of the ubiquitin-proteasome system show that introducing lysines at selected positions can alter ubiquitylation, protein turnover or function. These findings support a context-dependent model in which lysine deserts can limit the availability of ubiquitin acceptor sites within particular structural and enzymatic environments, rather than generally protecting entire proteins from modification or degradation. I discuss how lysine position, solvent accessibility, E3 ligase geometry and protein conformation determine the consequences of lysine introduction, and how N-terminal or non-lysine ubiquitylation as well as ubiquitin-independent proteolysis can bypass lysine depletion. I also consider the reported enrichment of lysine deserts in selected Actinobacteria and Mycobacterium phages, highlighting a testable Pup-proteasome adaptation hypothesis. Finally, I discuss potential functions beyond ubiquitylation and the methodological challenges of distinguishing selected lysine depletion from compositional bias or chance.
SN - 2296-889X
ER -