Semisynthesis of Isomerized Histone H4 Reveals Robustness and Vulnerability of Chromatin toward Molecular Aging.

ABSTRACT: Proteins are subject to aging in the form of spontaneous, nonenzymatic post-translational modifications (PTMs). One such PTM is the formation of the β-linked isomer l-isoaspartic acid (isoAsp) from aspartic acid (Asp) or asparagine residues, which tends to occur in long-lived proteins. Histones can exhibit half-lives on the order of 100 days, and unsurprisingly, isoAsp formation has been observed in nearly every histone family. Delineating the molecular consequences of isoAsp formation in histones is challenging due to the multitude of processes that occur on such time scales. To isolate the effects of a specific isoAsp modification thus necessitates precise in vitro characterization with well-defined substrates. Here, we adapt a protein semisynthesis approach to generate full-lengt

SUBMITTER: Zhang T 

PROVIDER: S-EPMC11826994 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature