Post-translational modification

A post-translational modification is a chemical change to a protein after its synthesis, such as phosphorylation or protein lipidation. It can change activity, stability, localization or partner binding without changing the encoded sequence.

ADP-ribosylation transfers an ADP-ribose group from NAD+ to a target, commonly a protein, with release of nicotinamide. It is a post-translational modification distinct from phosphorylation: the transferred chemical group is different, as are the enzymes that add or remove it. A modification can alter a target's activity or interactions without changing its encoded protein sequence. ^[ref]

The cholera toxin experiments linked NAD+-dependent modification of a membrane-associated protein to persistent activation of adenylyl cyclase. They provide a concrete example of how a covalent chemical change can amplify a cellular signal. Other ADP-ribosylation systems have different targets and outcomes, so the chemical name alone does not specify one biological response.

A covalent modification of a histone. Its genomic distribution and associated regulatory state do not by themselves specify chromatin accessibility or causation.

Histone methylation adds methyl groups to selected residues of histones. The position and number of methyl groups affect which binding partners recognize the mark. H3K4 methylation, H3K9 methylation and H3K27 trimethylation therefore cannot be treated as one interchangeable signal. Their distributions can be associated with different transcriptional states, and direct causation requires more than correlation between a mark and gene expression. ^[ref]

H3K27 methylation is addition of one or more methyl groups to the side chain of lysine 27 in histone H3. Mono-, di- and trimethylated states are different chemical states; a measurement of one is not automatically a measurement of the others. H3K27 trimethylation is particularly associated with Polycomb-mediated gene silencing. ^[ref]

A mechanistic test distinguishes correlation from catalysis. A purified complex can be supplied with histones and a methyl donor to test transfer, while changing a catalytic region tests whether that activity depends on an intact enzyme. In a cell, the distribution of the mark also depends on recruitment, removal and replacement of histones, not only on total enzyme abundance.

A chromatin complex that catalyses H3K27 methylation, with locus-specific recruitment and developmental functions.

Its catalytic activity deposits H3K27 methylation, including the trimethylated state associated with many repressed developmental genes. Recruitment and recognition of modified chromatin can stabilize a regulatory state while retaining the possibility of later reversal. ^[ref]

A plant histone methyltransferase participating in the reinforcing relationship between H3K9 methylation and methylated DNA.

A plant histone methyltransferase participating in the reinforcing relationship between H3K9 methylation and methylated DNA.

A plant histone methyltransferase participating in the reinforcing relationship between H3K9 methylation and methylated DNA.

H3K4 methylation modifies lysine 4 of histone H3 with one, two or three methyl groups. The states have different genomic distributions; trimethylation is often enriched near active transcription start regions. A mark can recruit binding factors or reflect ongoing regulatory activity, so enrichment does not by itself prove that the modification initiated transcription. State, genomic location and experimental perturbation are all needed for a mechanistic claim. ^[ref]

H3K27 trimethylation adds three methyl groups to lysine 27 of histone H3, conventionally H3K27me3. It is associated with Polycomb-linked repression of developmental genes in many eukaryotes. Deposition and removal help regulate the persistence of a chromatin state. A broad marked domain describes a molecular state; demonstrating that the mark is required for repression at a particular gene needs a perturbation that separates it from associated factors. ^[ref]

Protein deamidation converts an amide-bearing side chain, commonly asparagine or glutamine, into a carboxyl-containing product. It can occur spontaneously or through catalysis and can alter charge, structure or molecular interactions. Some asparagine reactions also produce an altered backbone linkage, making the product chemically more complex than a simple residue replacement. Sample handling and elapsed time can therefore affect the observed modification pattern. ^[ref]

The fraction of molecules modified at a specified site under specified conditions. Occupancies at separate sites do not alone establish the joint distribution of modifications across intact proteoforms.