Nucleotide exchange factors (NEFs) are proteins that stimulate the exchange (replacement) of nucleoside diphosphates for nucleoside triphosphates bound to other proteins.

Function

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Many cellular proteins cleave (hydrolyze) nucleoside triphosphates–adenosine triphosphate (ATP) or guanosine triphosphate (GTP)–to their diphosphate forms (ADP and GDP) as a source of energy and to drive conformational changes. These changes in turn affect the structural, enzymatic, or signalling properties of the protein.

Nucleotide exchange factors actively assist in the exchange of depleted nucleoside diphosphates for fresh nucleoside triphosphates. NEFs are specific for the nucleotides they exchange (ADP or GDP, but not both) and are often specific to a single protein or class of proteins with which they interact.

Adenine NEFs

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Guanine NEFs

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Guanine NEFs (GEFs) are implicated in addressing system of vesicular transport. For example, Rab is GDP bound and inactive in the cytosol before contact with GEF. The membrane bound GEF catalyses the removal of GDP and GDI (GDP dissociation inhibitor) and their replacement with GTP. This allows the Rab protein to bind budding vesicles (e.g. clathrin coated vesicles). Un-coating of the vesicle allows an interaction between Rab and Rab effector (at the target site) which aids SNARE protein interactions.

"Son of Sevenless" (SOS) is a GEF that is important in the cell growth-regulatory MAPK/ERK pathway.

See also

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Nucleoside-diphosphate kinase