peptidyl-L-cysteine S-palmitoylation

Definition

Target type: biologicalprocess

The covalent attachment of a palmitoyl group to a sulfur (S) atom within a cysteine residue to form peptidyl-S-palmitoyl-L-cysteine. [RESID:AA0106]

Peptidyl-L-cysteine S-palmitoylation is a post-translational modification that involves the covalent attachment of palmitic acid, a 16-carbon saturated fatty acid, to a cysteine residue within a protein. This process plays a crucial role in regulating protein function, localization, and interactions. Palmitoylation typically occurs on cysteine residues located near the N-terminus or within transmembrane domains of proteins. The addition of a palmitate moiety can significantly alter the hydrophobicity of a protein, influencing its interaction with cellular membranes.

The enzymatic machinery responsible for palmitoylation involves a family of enzymes known as palmitoyl acyltransferases (PATs). PATs utilize a two-step mechanism to catalyze the transfer of palmitate from a palmitoyl-CoA donor to a target cysteine residue. Firstly, PATs bind to both palmitoyl-CoA and the substrate protein, bringing them into close proximity. Next, the enzyme facilitates the transfer of the palmitate moiety from palmitoyl-CoA to the cysteine residue, resulting in the formation of a thioester bond. The process is highly dynamic and reversible, with palmitoylation and depalmitoylation occurring continuously in cells. Depalmitoylation, the removal of palmitate from a protein, is mediated by a distinct set of enzymes called thioesterases.

Palmitoylation exerts a profound influence on protein function and localization. The attachment of palmitate can enhance protein membrane association, facilitating protein trafficking, signaling, and interactions with other membrane-bound proteins. In some instances, palmitoylation can induce conformational changes within a protein, altering its activity.

Examples of cellular processes regulated by palmitoylation include:
* **Signaling pathways:** Palmitoylation plays a pivotal role in regulating signaling pathways by modulating the activity of signaling proteins. For example, palmitoylation of Ras proteins, small GTPases involved in cell growth and proliferation, is crucial for their membrane association and signaling activity.
* **Protein trafficking:** Palmitoylation can direct proteins to specific cellular compartments, including the plasma membrane, endoplasmic reticulum, and Golgi apparatus. The palmitate moiety serves as a membrane anchor, facilitating protein translocation and localization.
* **Protein-protein interactions:** Palmitoylation can promote protein-protein interactions by facilitating the association of palmitoylated proteins with other membrane-bound proteins or lipid rafts.

The intricate interplay between palmitoylation and depalmitoylation is crucial for maintaining cellular homeostasis and responding to external stimuli. Dysregulation of palmitoylation has been implicated in various disease states, including cancer, neurodegenerative disorders, and cardiovascular diseases. Further understanding of the molecular mechanisms underlying palmitoylation and its roles in cellular processes holds great promise for the development of novel therapeutic strategies for a range of human diseases.'
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Proteins (1)

Compounds (1)