Lipid-anchored protein
Lipid-anchored proteins (also known as lipid-linked proteins) are
The lipid groups play a role in protein interaction and can contribute to the function of the protein to which it is attached.[2] Furthermore, the lipid serves as a mediator of membrane associations or as a determinant for specific protein-protein interactions.[3] For example, lipid groups can play an important role in increasing molecular hydrophobicity. This allows for the interaction of proteins with cellular membranes and protein domains.[4] In a dynamic role[clarification needed], lipidation can sequester a protein away from its substrate to inactivate the protein and then activate it by substrate presentation.
Overall, there are three main types of lipid-anchored proteins which include prenylated proteins, fatty acylated proteins and glycosylphosphatidylinositol-linked proteins (GPI).[2][5] A protein can have multiple lipid groups covalently attached to it, but[clarification needed] the site where the lipids bind to the protein depends both on the lipid group and protein.[2]
Prenylated proteins
The prenylation motif “CaaX box” is the most common prenylation site in proteins, that is, the site where farnesyl or geranylgeranyl covalently attach.[2][3] In the CaaX box sequence, the C represents the cysteine that is prenylated, the A represents any aliphatic amino acid and the X determines the type of prenylation that will occur. If the X is an Ala, Met, Ser or Gln the protein will be farnesylated via the farnesyltransferase enzyme and if the X is a Leu then the protein will be geranylgeranylated via the geranylgeranyltransferase I enzyme.[3][4] Both of these enzymes are similar with each containing two subunits.[7]
Roles and function
Prenylated proteins are particularly important for eukaryotic cell growth, differentiation and morphology.
Some important prenylation chains that are involved in the HMG-CoA reductase metabolic pathway[1] are geranylgeraniol, farnesol and dolichol. These isoprene polymers (e.g. geranyl pyrophosphate and farnesyl pyrophosphate) are involved in the condensations via enzymes such as prenyltransferase that eventually cyclizes to form cholesterol.[2]
Fatty acylated proteins
Fatty acylated proteins are proteins that have been post-translationally modified to include the covalent attachment of fatty acids at certain amino acid residues.[11][12] The most common fatty acids that are covalently attached to the protein are the saturated myristic (14-carbon) acid and palmitic acid (16-carbon). Proteins can be modified to contain either one or both of these fatty acids.[11]
N-myristoylation
N-myristoylation (i.e. attachment of myristic acid) is generally an irreversible protein modification that typically occurs during protein synthesis
S-palmitoylation
S-palmitoylation (i.e. attachment of palmitic acid) is a reversible protein modification in which a palmitic acid is attached to a specific cysteine residue via
Palmitoylation mediates the affinity of a protein for
GPI proteins
Glycosylphosphatidylinositol-anchored proteins (GPI-anchored proteins) are attached to a GPI complex molecular group via an
Roles and function
The sugar residues in the tetrasaccaride and the fatty acid residues in the
References
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- ^ Dityatev, Alexander (2006). El-Husseini, Alaa (ed.). Molecular Mechanisms of Synaptogenesis. New York: Springer. pp. 72–75.
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External links
- Media related to Lipid-anchored protein at Wikimedia Commons