Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies

Abstract

Protein lipidation, including cysteine prenylation, N-terminal glycine myristoylation, cysteine palmitoylation, and serine and lysine fatty acylation, occurs in many proteins in eukaryotic cells and regulates numerous biological pathways, such as membrane trafficking, protein secretion, signal transduction, and apoptosis. We provide a comprehensive review of protein lipidation, including descriptions of proteins known to be modified and the functions of the modifications, the enzymes that control them, and the tools and technologies developed to study them. We also highlight key questions about protein lipidation that remain to be answered, the challenges associated with answering such questions, and possible solutions to overcome these challenges.

Histone/protein deacetylase inhibitor therapy for enhancement of Foxp3+ T-regulatory cell function posttransplantation

“…Their ability to function as lysine deacylases, removing fatty acid modifications from proteins, has not been reported, though other HDACs with limited deacetylase activity, such as HDAC8, 10 and 11, are active in this regard. 36 …”

Far from Inert: Membrane Lipids Possess Intrinsic Reactivity That Has Consequences for Cell Biology

“…It is well established that lipidation of membrane proteins can drive local conformational changes and influence both the membrane affinity of a protein and its lateral distribution within the membrane . Lipidation can have even more pronounced effects on peptides that, when compared to proteins, are more likely to be unfolded when non‐lipidated due to their smaller size and undergo a more pronounced overall change in hydrophobicity (or amphiphilicity) following the addition of a fatty acyl group.…”

Synthetic Strategies for Artificial Lipidation of Functional Proteins

“…In nature, co‐translational or post‐translational lipidation of proteins occurs in the cellular environment and regulates cellular programs such as cell proliferation, apoptosis, oncogenesis, differentiation, membrane trafficking, protein secretion, and signal transduction . The type of lipid plays an important role in the interaction of lipid–protein conjugates in the cellular membrane.…”

“…Native post‐translational lipid modification of a protein renders a lipid moiety composed of fatty acids, isoprenoids, sterols, phospholipids, or glycosylphosphatidyl inositol (GPI), which acts as a cellular membrane anchor (Figure ) . The type of lipid on the protein determines the function of the lipidated form, which is primarily governed by the hydrophobicity of the lipid as it modulates the conformational change of the lipidated protein and its association with the membrane .…”