Geranylgeranylation: Difference between revisions

Geranylgeranylation
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Latest revision as of 20:21, 30 December 2024

Geranylgeranylation is a form of prenylation, a post-translational modification of proteins. This process involves the addition of a geranylgeranyl group to a cysteine residue at or near the C-terminus of a protein. Geranylgeranylation is crucial for the proper functioning of a variety of proteins, including members of the Rho family of GTPases, which are involved in cell signaling and cytoskeletal dynamics.

Mechanism[edit]

Geranylgeranylation is catalyzed by the enzyme geranylgeranyltransferase. This enzyme transfers a geranylgeranyl moiety from geranylgeranyl pyrophosphate (GGPP) to the target protein. The modification typically occurs at a CAAX motif, where "C" is a cysteine, "A" is an aliphatic amino acid, and "X" is any amino acid that determines the type of prenylation.

Biological Significance[edit]

The addition of a geranylgeranyl group increases the hydrophobicity of the protein, facilitating its association with cell membranes. This membrane association is essential for the protein's biological activity. For example, geranylgeranylation of Rho GTPases is necessary for their role in regulating the actin cytoskeleton, which is important for cell migration, cell division, and cell shape.

Clinical Implications[edit]

Defects in geranylgeranylation can lead to various diseases. For instance, improper prenylation of proteins has been implicated in certain cancers and cardiovascular diseases. Inhibitors of geranylgeranyltransferase are being explored as potential therapeutic agents for these conditions.

References[edit]

External Links[edit]

[Geranylgeranylation on Wikipedia](https://en.wikipedia.org/wiki/Geranylgeranylation)

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-'''Geranylgeranylation''' is a type of [[protein prenylation]], a post-translational modification of proteins. It involves the addition of a 20-carbon [[geranylgeranyl]] group to the [[C-terminus]] of a protein, typically to a cysteine residue. This process is crucial for the proper functioning of the protein and its localization within the cell.
-== Process ==
+{{Infobox medical condition
+| name = Geranylgeranylation
+| image = <!-- Image removed -->
+| caption = <!-- Caption removed -->
+| field = Biochemistry
+}}
-Geranylgeranylation is catalyzed by [[geranylgeranyl transferase]] enzymes. There are two types of these enzymes: type I and type II. Type I enzymes add a geranylgeranyl group to the cysteine residue of a protein with a specific four-amino-acid sequence at the C-terminus, known as a [[CAAX motif]]. Type II enzymes add a geranylgeranyl group to the cysteine residue of a protein with a different C-terminal sequence.
+'''Geranylgeranylation''' is a form of [[prenylation]], a post-translational modification of proteins. This process involves the addition of a [[geranylgeranyl group]] to a [[cysteine]] residue at or near the C-terminus of a protein. Geranylgeranylation is crucial for the proper functioning of a variety of proteins, including members of the [[Rho family of GTPases]], which are involved in [[cell signaling]] and [[cytoskeletal dynamics]].
-The process of geranylgeranylation begins with the synthesis of geranylgeranyl pyrophosphate (GGPP), a 20-carbon molecule derived from [[isopentenyl pyrophosphate]] (IPP) and [[dimethylallyl pyrophosphate]] (DMAPP). This synthesis is catalyzed by the enzyme [[geranylgeranyl diphosphate synthase]].
+== Mechanism ==
+Geranylgeranylation is catalyzed by the enzyme [[geranylgeranyltransferase]]. This enzyme transfers a geranylgeranyl moiety from [[geranylgeranyl pyrophosphate]] (GGPP) to the target protein. The modification typically occurs at a [[CAAX motif]], where "C" is a cysteine, "A" is an aliphatic amino acid, and "X" is any amino acid that determines the type of prenylation.
-The GGPP molecule is then attached to the target protein by the geranylgeranyl transferase enzyme. This attachment occurs through a thioether bond between the sulfur atom of the cysteine residue and the terminal carbon atom of the GGPP molecule.
+== Biological Significance ==
+The addition of a geranylgeranyl group increases the hydrophobicity of the protein, facilitating its association with cell membranes. This membrane association is essential for the protein's biological activity. For example, geranylgeranylation of [[Rho GTPases]] is necessary for their role in [[regulating the actin cytoskeleton]], which is important for [[cell migration]], [[cell division]], and [[cell shape]].
-== Function ==
+== Clinical Implications ==
+Defects in geranylgeranylation can lead to various diseases. For instance, improper prenylation of proteins has been implicated in certain [[cancer]]s and [[cardiovascular diseases]]. Inhibitors of geranylgeranyltransferase are being explored as potential therapeutic agents for these conditions.
-Geranylgeranylation plays a crucial role in the localization and function of several proteins. It is particularly important for the function of small [[GTPases]], such as those in the [[Ras superfamily]]. These proteins are involved in a variety of cellular processes, including cell growth, differentiation, and apoptosis.
-In addition to GTPases, several other proteins are known to undergo geranylgeranylation. These include [[nuclear lamins]], which are important for maintaining the structure of the [[nuclear envelope]], and [[peripheral membrane proteins]], which are associated with the plasma membrane.
-== Clinical significance ==
-Abnormalities in geranylgeranylation have been linked to a variety of diseases, including [[cancer]], [[cardiovascular disease]], and [[progeria]], a premature aging syndrome. Inhibitors of geranylgeranylation, such as [[statins]] and [[bisphosphonates]], are currently used in the treatment of these diseases.
-[[File:Geranylgeranylation.png|thumb|right|300px|Geranylgeranylation of a protein. The geranylgeranyl group (in red) is attached to the cysteine residue of the protein (in blue).]]
-== See also ==
+== See Also ==
 * [[Prenylation]]
 * [[Farnesylation]]
-* [[Protein targeting]]
+* [[Protein modification]]
-* [[Post-translational modification]]
 == References ==
+<references />
-<references />
+== External Links ==
+* [Geranylgeranylation on Wikipedia](https://en.wikipedia.org/wiki/Geranylgeranylation)
-{{protein-stub}}
+[[Category:Biochemistry]]
-[[Category:Protein modifications]]
 [[Category:Post-translational modification]]
-[[Category:Cell biology]]
+[[Category:Cell signaling]]
-[[Category:Biochemistry]]