What are GAP and GEF in biochemistry


English: Ras-related nuclear protein, GTP-binding nuclear protein Ran

1 definition

Ran is a monomeric G-protein that binds the nucleotide GTP and regulates the import and export of proteins at the nucleus.

2 background

Transcription takes place in the nucleus, while translation takes place in the cytosol. Proteins that are intended for the cell nucleus must be imported post-translationally. The transport takes place through the nuclear pores in the nuclear membrane. At the same time, certain proteins, such as transcription factors, have to be exported from the nucleus under certain conditions.

3 biochemistry

Ran has a molecular weight of 25 kDa and can bind GTP or GDP. The GTPase activity (hydrolysis of GTP with cleavage of phosphate) of the protein is determined by a Ran-GAP (GTPase activating protein) activated. The exchange of GDP for GTP is carried out by a Ran-GEF (Guanine nucleotide exchange factor) induced. Ran-GEF is bound to the chromatin and thus localized in the cell nucleus. In contrast, Ran-GAP is bound to the outer side of the nuclear membrane. Due to the specific localization of GEF and GAP, Ran is predominantly in the GTP form in the cell nucleus, but in the GDP form in the cytosol.

4 function

4.1 Core import

Nuclear proteins carry a specific nuclear localization sequence with predominantly positively charged amino acids, which they mark for import. Using this sequence, they bind the transport receptors Importin α and Importin β in the cytosol, which transport the protein through the nuclear pores into the cell nucleus. Ran-GTP stimulates the dissociation of the receptor-protein complex and binds the receptor itself. This complex diffuses into the cytosol. Here Ran-GAP activates the small GTPase and Ran-GDP is created, which releases the receptor again. Ran-GDP gets back into the core. There Ran-GEF replaces the GDP with a GTP - thus the cycle is completed.

4.2 Core export

Analogous to imports, some proteins have core export sequences with predominantly hydrophobic amino acids. Export receptors bind proteins via this sequence and, together with Ran-GTP, form an export complex that diffuses into the cytosol. The complex is dissolved with the aid of the Ran-GAP by activating the GTPase activity of the Ran. The complex breaks down into the protein to be transported, the export receptor and Ran-GDP. The export receptor and Ran-GDP get back into the core. There - as described above - the GDP is exchanged for a GTP by means of Ran-GEF.