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Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.

Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered incomplete enzymes. They need additional proteins called Rab regulators, such as Guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and, Guanosine dissociation inhibitors (GDIs).

In its inactive form, Rab-GDP is associated with GDI, which keeps the protein in the cytosol. GDI displacement factors help GDI dissociation and present Rab to the membrane-bound GEF for GDP/GTP exchange. On being activated by GEF, Rab-GTP is localized to the membrane by Rab Escort Proteins, which allows geranyl transferases to add a prenyl group to the Rab, anchoring it to the membrane. GTP-hydrolysis activating proteins or GAPs bind Rab-GTP and accelerate GTP hydrolysis, which returns Rab to its inactive state.

Biochemical defects in Rab regulation can lead to infections and congenital diseases. Therefore, studying molecular interactions between Rab effectors and other Rab protein machinery provides an understanding of cellular compartments' distribution through vesicle movement regulation. Mechanistic details of the structural changes that Rabs and their regulators, GEFs, GAPs, and GDIs, undergo can be used to identify transient protein interfaces that drugs can target.

Теги
Rab ProteinsMonomeric GTPasesVesicle TransportDockingFusionGDP boundGTP boundRab RegulatorsGuanine Nucleotide Exchange Factors GEFsGTPase Activating Proteins GAPsGuanosine Dissociation Inhibitors GDIsRab GDPGDI Displacement FactorsRab Escort ProteinsGeranyl TransferasesGTP hydrolysis Activating ProteinsBiochemical DefectsMolecular InteractionsCellular Compartments Distribution

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