Protein lipid modifications--More than just a greasy ballast

Proteomics. 2016 Mar;16(5):759-82. doi: 10.1002/pmic.201500353.


Covalent lipid modifications of proteins are crucial for regulation of cellular plasticity, since they affect the chemical and physical properties and therefore protein activity, localization, and stability. Most recently, lipid modifications on proteins are increasingly attracting important regulatory entities in diverse signaling events and diseases. In all cases, the lipid moiety of modified proteins is essential to allow water-soluble proteins to strongly interact with membranes or to induce structural changes in proteins that are critical for elemental processes such as respiration, transport, signal transduction, and motility. Until now, roughly about ten lipid modifications on different amino acid residues are described at the UniProtKB database and even well-known modifications are underrepresented. Thus, it is of fundamental importance to develop a better understanding of this emerging and so far under-investigated type of protein modification. Therefore, this review aims to give a comprehensive and detailed overview about enzymatic and nonenzymatic lipidation events, will report their role in cellular biology, discuss their relevancy for diseases, and describe so far available bioanalytical strategies to analyze this highly challenging type of modification.

Keywords: Acylation; Cell biology; Cholesterylation; Electrophiles; Lipidation; Prenylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Lipid Metabolism / physiology*
  • Lipids / chemistry
  • Lipoylation / physiology*
  • Protein Prenylation / physiology*
  • Proteins / metabolism*


  • Lipids
  • Proteins