Authors
Natalia A Szulc
Published in
Frontiers in molecular biosciences. Volume 13. Pages 1959694. Epub Oct 12, 2026.
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.
PMID:
42928854
Bibliographic data and abstract were imported from PubMed on 26 Oct 2026.
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