Sandbox Reserved 709: Difference between revisions

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Import through NPC follows different steps :

* '''Step 1 : ''' The NLS of the protein binds the NLS-binding site of importin α.

* '''Step 1 :''' The NLS of the protein binds the NLS-binding site of importin α.

* '''Step 2 : ''' Importin α binds to importin β because of its importin β binding domain (IBB). ~~Then importin~~ β binds to some fibrils of the NPC. These fibrils contain a lot of short amino-acid repeats that contain phenylalanine and glycine and are therefore called FG-repeats.

* '''Step 2 :''' Importin α binds to importin β because of its importin β binding domain (IBB). Importin β binds to some fibrils of the NPC. These fibrils contain a lot of short amino-acid repeats that contain phenylalanine and glycine and are therefore called FG-repeats.

* '''Step 3 : ''' The complex '''cargo:importin α:importin β''' move along the NPC by repeatedly binding, dissociating and re-binding to adjacent FG-repeat sequences.

* '''Step 3 :''' The complex '''cargo:importin α:importin β''' move along the NPC by repeatedly binding, dissociating and re-binding to adjacent FG-repeat sequences.

===Cargo release and protein recycling===

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Once the import complex enters the nucleus, it must be dissociated to release the cargo protein. Then, importin α must be recycled to the cytoplasm.

* '''Step 4 :''' Cargo release is driven by '''Ran''', a G-protein that is found in Ran-GTP form in the nucleus due to a higher rate of RanGEF than RanGAP in chromatin. It binds to importin β, causing an important change in shape and reducing importin β affinity for importin α IBB.

* '''Step 5 :''' Importin β can pass through the NPC thanks to Ran-GTP. A Ran-BP (~~‘’Ran~~-Binding ~~Protein’’~~) is a major component of the NPC’s cytoplasmic filaments. Thus, Ran-GTP is not released in the cytoplasm, but is still bound with importin β to the NPC. Ran-BP is also able to bind to a RanGAP. Finally, RanGAP locally promotes hydrolysis of Ran-GTP into Ran-GDP, leading to its own release, and importin β release by the same.

* '''Step 5 :''' Importin β can pass through the NPC thanks to Ran-GTP. A Ran-BP (''Ran-Binding Protein'') is a major component of the NPC’s cytoplasmic filaments. Thus, Ran-GTP is not released in the cytoplasm, but is still bound with importin β to the NPC. Ran-BP is also able to bind to a RanGAP. Finally, RanGAP locally promotes hydrolysis of Ran-GTP into Ran-GDP, leading to its own release, and importin β release by the same.

* '''Step 6 :''' '''Nup50''' (also called '''Npap60'''), a nucleoplasmin, weakens the link between importin α and the NLS of the cargo. Thus the cargo protein is now free in the nucleoplasm.

* '''Step 7 :''' Importin α can’t leave the nucleus only with the help of Ran-GTP. It needs also interaction with '''CAS''' (''Cellular Apoptosis Susceptibility'' protein), an '''exportin''' which is similar in shape to importin β. Binding between CAS and importin α is favoured by interactions with Nup50. The newly formed importin α, CAS ~~and~~ Ran-GTP complex is able to interact with nucleoplasmins of NPC, and once in the cytoplasm, Ran-GTP is hydrolysed into Ran-GDP. The complex splits, and importin α is now ready for a new import cycle.

* '''Step 7 :''' Importin α can’t leave the nucleus only with the help of Ran-GTP. It needs also interaction with '''CAS''' (''Cellular Apoptosis Susceptibility'' protein), an '''exportin''' which is similar in shape to importin β. Binding between CAS and importin α is favoured by interactions with Nup50.

* '''Step 8 :'''The newly formed '''importin α:CAS:Ran-GTP''' complex is able to interact with nucleoplasmins of NPC, and once in the cytoplasm, Ran-GTP is hydrolysed into Ran-GDP (''see '''Step 5''' for details''). The complex splits, and importin α is now ready for a new import cycle.

==Importin α structure==

Sandbox Reserved 709: Difference between revisions

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@@ Line 28: / Line 28: @@
 Import through NPC follows different steps :
-* '''Step 1 : ''' The NLS of the protein binds the NLS-binding site of importin α.
+* '''Step 1 :''' The NLS of the protein binds the NLS-binding site of importin α.
-* '''Step 2 : ''' Importin α binds to importin β because of its importin β binding domain (IBB). Then importin β binds to some fibrils of the NPC. These fibrils contain a lot of short amino-acid repeats that contain phenylalanine and glycine and are therefore called FG-repeats.
+* '''Step 2 :''' Importin α binds to importin β because of its importin β binding domain (IBB). Importin β binds to some fibrils of the NPC. These fibrils contain a lot of short amino-acid repeats that contain phenylalanine and glycine and are therefore called FG-repeats.
-* '''Step 3 : ''' The complex '''cargo:importin α:importin β''' move along the NPC by repeatedly binding, dissociating and re-binding to adjacent FG-repeat sequences.
+* '''Step 3 :''' The complex '''cargo:importin α:importin β''' move along the NPC by repeatedly binding, dissociating and re-binding to adjacent FG-repeat sequences.
 ===Cargo release and protein recycling===
@@ Line 36: / Line 38: @@
 Once the import complex enters the nucleus, it must be dissociated to release the cargo protein. Then, importin α must be recycled to the cytoplasm.
 * '''Step 4 :''' Cargo release is driven by '''Ran''', a G-protein that is found in Ran-GTP form in the nucleus due to a higher rate of RanGEF than RanGAP in chromatin. It binds to importin β, causing an important change in shape and reducing importin β affinity for importin α IBB.
-* '''Step 5 :''' Importin β can pass through the NPC thanks to Ran-GTP. A Ran-BP (‘’Ran-Binding Protein’’) is a major component of the NPC’s cytoplasmic filaments. Thus, Ran-GTP is not released in the cytoplasm, but is still bound with importin β to the NPC. Ran-BP is also able to bind to a RanGAP. Finally, RanGAP locally promotes hydrolysis of Ran-GTP into Ran-GDP, leading to its own release, and importin β release by the same.
+* '''Step 5 :''' Importin β can pass through the NPC thanks to Ran-GTP. A Ran-BP (''Ran-Binding Protein'') is a major component of the NPC’s cytoplasmic filaments. Thus, Ran-GTP is not released in the cytoplasm, but is still bound with importin β to the NPC. Ran-BP is also able to bind to a RanGAP. Finally, RanGAP locally promotes hydrolysis of Ran-GTP into Ran-GDP, leading to its own release, and importin β release by the same.
 * '''Step 6 :''' '''Nup50''' (also called '''Npap60'''), a nucleoplasmin, weakens the link between importin α and the NLS of the cargo. Thus the cargo protein is now free in the nucleoplasm.
-* '''Step 7 :''' Importin α can’t leave the nucleus only with the help of Ran-GTP. It needs also interaction with '''CAS''' (''Cellular Apoptosis Susceptibility'' protein), an '''exportin''' which is similar in shape to importin β. Binding between CAS and importin α is favoured by interactions with Nup50. The newly formed importin α, CAS and Ran-GTP complex is able to interact with nucleoplasmins of NPC, and once in the cytoplasm, Ran-GTP is hydrolysed into Ran-GDP. The complex splits, and importin α is now ready for a new import cycle.
+* '''Step 7 :''' Importin α can’t leave the nucleus only with the help of Ran-GTP. It needs also interaction with '''CAS''' (''Cellular Apoptosis Susceptibility'' protein), an '''exportin''' which is similar in shape to importin β. Binding between CAS and importin α is favoured by interactions with Nup50.
+* '''Step 8 :'''The newly formed '''importin α:CAS:Ran-GTP''' complex is able to interact with nucleoplasmins of NPC, and once in the cytoplasm, Ran-GTP is hydrolysed into Ran-GDP (''see '''Step 5''' for details''). The complex splits, and importin α is now ready for a new import cycle.
 ==Importin α structure==