Sandbox Reserved 709: Difference between revisions

Line 52:

Here, as the structure begins at the amino acid number 70, we cannot see the IBB which is located in the 2-60 region.

* '''A 50kDa C-terminal''' <scene name='Sandbox_Reserved_709/Importin_nlsbs/1'>NLS binding sites</scene> contained in <scene name='Sandbox_Reserved_709/Importin_arm/3'>10 tandem armadillo (Arm) repeats</scene>. These arm repeat domains have an elongated superhelical structure and each of them contains 3 α-helices (H1, H2, H3). Together, H3 helices define the inner concave surface of the protein and the NLS-binding site. The main chain of the cNLs runs antiparallel to the direction of the importin α superhelix, with the cNLS backbone interacting with an array of conserved asparagine residues in consecutive Arm repeats on the importin α surface.In fact there are two NLS-binding sites : a major one and a minor one. Thus, monopartite cNLSs are able to bind at two distinct sites on importin α (with a preference for the major site). Bipartite cNLSs simultaneously interact with both binding sites, with the larger C-terminal basic cluster binding to the major site (located in Arm repeats 2-4) and the smaller upstream cluster binding to the minor site (located in Arm repeats 6-8).<ref>PMID:22248489</ref>

* '''A 50kDa C-terminal''' <scene name='Sandbox_Reserved_709/Importin_nlsbs/2'>NLS binding sites</scene> contained in <scene name='Sandbox_Reserved_709/Importin_arm/5'>10 tandem armadillo (Arm) repeats</scene>. These arm repeat domains have an elongated superhelical structure and each of them contains 3 α-helices (H1, H2, H3). Together, H3 helices define the inner concave surface of the protein and the NLS-binding site. The main chain of the cNLs runs antiparallel to the direction of the importin α superhelix, with the cNLS backbone interacting with an array of conserved asparagine residues in consecutive Arm repeats on the importin α surface.In fact there are two NLS-binding sites : a major one and a minor one. Thus, monopartite cNLSs are able to bind at two distinct sites on importin α (with a preference for the major site). Bipartite cNLSs simultaneously interact with both binding sites, with the larger C-terminal basic cluster binding to the major site (located in Arm repeats 2-4) and the smaller upstream cluster binding to the minor site (located in Arm repeats 6-8).<ref>PMID:22248489</ref>

Here you can see a <scene name='Sandbox_Reserved_709/Nls_basic/1'>NLS </scene>bound to the NLS-binding site of importin α.

Here you can see a <scene name='Sandbox_Reserved_709/Nls_basic/2'>NLS </scene>bound to the NLS-binding site of importin α.

* '''A NLS'''. Thus, importin α belongs to the group of proteins containing both a ligand (NLS) and a cognate receptor (NLS-binding site). That’s why it could have a possibility of autologous ligand-receptor interactions. Nevertheless, it has been shown that NLS of importin α overlaps with the IBB. Thereby, binding of importin β to importin α covers the NLS of importin α preventing autologous ligand receptor interactions. <ref>PMID:8692858</ref>

Line 69:

Nup50 (''Nucleoporin 50 kDa'', about 450 aminoacids) is a part of the NPCs, in the nucleoplasmic side. It is able to bind to <scene name='Sandbox_Reserved_709/Importin/1'> importin α</scene>thanks to ~~its~~ <scene name='Sandbox_Reserved_709/Nup50/1'>~~N-terminus~~ </scene> (''only 40 first aminoacids represented on the structure''). ~~There are two binding sites for Nup50 on importin α :~~

Nup50 (''Nucleoporin 50 kDa'', about 450 aminoacids) is a part of the NPCs, in the nucleoplasmic side. It is able to bind to <scene name='Sandbox_Reserved_709/Importin/2'> importin α </scene>thanks to <scene name='Sandbox_Reserved_709/Nup50/3'>two binding segments</scene> on its N-terminus (''only 40 first aminoacids represented on the structure'').

* The first one ~~overlaps with~~ the minor NLS binding site. This binding is allowed by the two basic aminoacids<scene name='Sandbox_Reserved_709/Nup_bindingnls/1'>Lys3 and Arg4</scene> of Nup50. In fact, the positive charge will establish bonds with acidic aminoacids of the NLS binding site, just as an NLS-containing cargo would do. In presence of Nup50, the complex importin α:NLS dissociation rate is higher than the one of spontaneous dissociation : there is a competition between Nup50 and NLS, whose affinities for the NLS minor binding site are in the same order of magnitude.

* The first one (''1-15'') binds to the '''minor NLS binding site''' of importin α. This binding is allowed by the '''two basic aminoacids'''<scene name='Sandbox_Reserved_709/Nup_bindingnls/1'>Lys3 and Arg4</scene> of Nup50. In fact, the positive charge will establish bonds with acidic aminoacids of the NLS binding site, just as an NLS-containing cargo would do. In presence of Nup50, the complex importin α:NLS dissociation rate is higher than the one of spontaneous dissociation : there is a '''competition''' between Nup50 and NLS, whose affinities for the NLS minor binding site are in the same order of magnitude.

* The second one binds to the C-terminus of importin α.

* The second one (''24-46'') binds to the '''C-terminus''' of importin α. Nup50 basic residues 41-46 ('''KKAKRR''') are directed by the formation of two turns of an α helix (''31-36'' SEEVMK) towards an <scene name='Sandbox_Reserved_709/Nup50_bindingcas/1'>acidic surface</scene> on ARM10. Those electrostatic interactions are essential for the binding of Nup50. Indeed, replacing residues 41-46 by Ala makes the binding undetectable. Furthermore, this binding overlaps the CAS and the Ran binding sites, explaining why interaction between Nup50 and importin is crucial for building the export complex.

The chain between the two binding segments is rich in acidic residues, and seems to work as a flexible linker between those two sites.

Sandbox Reserved 709: Difference between revisions

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@@ Line 52: / Line 52: @@
 Here, as the structure begins at the amino acid number 70, we cannot see the IBB which is located in the 2-60 region.
-* '''A 50kDa C-terminal''' <scene name='Sandbox_Reserved_709/Importin_nlsbs/1'>NLS binding sites</scene> contained in <scene name='Sandbox_Reserved_709/Importin_arm/3'>10 tandem armadillo (Arm) repeats</scene>. These arm repeat domains have an elongated superhelical structure and each of them contains 3 α-helices (H1, H2, H3). Together, H3 helices define the inner concave surface of the protein and the NLS-binding site.  The main chain of the cNLs runs antiparallel to the direction of the importin α superhelix, with the cNLS backbone interacting with an array of conserved asparagine residues in consecutive Arm repeats on the importin α surface.In fact there are two NLS-binding sites : a major one and a minor one. Thus, monopartite cNLSs are able to bind at two distinct sites on importin α (with a preference for the major site). Bipartite cNLSs simultaneously interact with both binding sites, with the larger C-terminal basic cluster binding to the major site (located in Arm repeats 2-4) and the smaller upstream cluster binding to the minor site (located in Arm repeats 6-8).<ref>PMID:22248489</ref>
+* '''A 50kDa C-terminal''' <scene name='Sandbox_Reserved_709/Importin_nlsbs/2'>NLS binding sites</scene> contained in <scene name='Sandbox_Reserved_709/Importin_arm/5'>10 tandem armadillo (Arm) repeats</scene>. These arm repeat domains have an elongated superhelical structure and each of them contains 3 α-helices (H1, H2, H3). Together, H3 helices define the inner concave surface of the protein and the NLS-binding site.  The main chain of the cNLs runs antiparallel to the direction of the importin α superhelix, with the cNLS backbone interacting with an array of conserved asparagine residues in consecutive Arm repeats on the importin α surface.In fact there are two NLS-binding sites : a major one and a minor one. Thus, monopartite cNLSs are able to bind at two distinct sites on importin α (with a preference for the major site). Bipartite cNLSs simultaneously interact with both binding sites, with the larger C-terminal basic cluster binding to the major site (located in Arm repeats 2-4) and the smaller upstream cluster binding to the minor site (located in Arm repeats 6-8).<ref>PMID:22248489</ref>
-Here you can see a <scene name='Sandbox_Reserved_709/Nls_basic/1'>NLS </scene>bound to the NLS-binding site of importin α.
+Here you can see a <scene name='Sandbox_Reserved_709/Nls_basic/2'>NLS </scene>bound to the NLS-binding site of importin α.
 * '''A NLS'''. Thus, importin α belongs to the group of proteins containing both a ligand (NLS) and a cognate receptor (NLS-binding site). That’s why it could have a possibility of autologous ligand-receptor interactions. Nevertheless, it has been shown that NLS of importin α overlaps with the IBB. Thereby, binding of importin β to importin α covers the NLS of importin α preventing autologous ligand receptor interactions. <ref>PMID:8692858</ref>
@@ Line 69: / Line 69: @@
-Nup50 (''Nucleoporin 50 kDa'', about 450 aminoacids) is a part of the NPCs, in the nucleoplasmic side. It is able to bind to <scene name='Sandbox_Reserved_709/Importin/1'> importin α</scene>thanks to its <scene name='Sandbox_Reserved_709/Nup50/1'>N-terminus </scene> (''only 40 first aminoacids represented on the structure''). There are two binding sites for Nup50 on importin α :
+Nup50 (''Nucleoporin 50 kDa'', about 450 aminoacids) is a part of the NPCs, in the nucleoplasmic side. It is able to bind to <scene name='Sandbox_Reserved_709/Importin/2'> importin α </scene>thanks to <scene name='Sandbox_Reserved_709/Nup50/3'>two binding segments</scene> on its N-terminus (''only 40 first aminoacids represented on the structure'').
-* The first one overlaps with the minor NLS binding site. This binding is allowed by the two basic aminoacids<scene name='Sandbox_Reserved_709/Nup_bindingnls/1'>Lys3 and Arg4</scene> of Nup50. In fact, the positive charge will establish bonds with acidic aminoacids of the NLS binding site, just as an NLS-containing cargo would do. In presence of Nup50, the complex importin α:NLS dissociation rate is higher than the one of spontaneous dissociation : there is a competition between Nup50 and NLS, whose affinities for the NLS minor binding site are in the same order of magnitude.
+* The first one (''1-15'') binds to the '''minor NLS binding site''' of importin α. This binding is allowed by the '''two basic aminoacids'''<scene name='Sandbox_Reserved_709/Nup_bindingnls/1'>Lys3 and Arg4</scene> of Nup50. In fact, the positive charge will establish bonds with acidic aminoacids of the NLS binding site, just as an NLS-containing cargo would do. In presence of Nup50, the complex importin α:NLS dissociation rate is higher than the one of spontaneous dissociation : there is a '''competition''' between Nup50 and NLS, whose affinities for the NLS minor binding site are in the same order of magnitude.
-* The second one binds to the C-terminus of importin α.
+* The second one (''24-46'') binds to the '''C-terminus''' of importin α. Nup50 basic residues 41-46 ('''KKAKRR''') are directed by the formation of two turns of an α helix (''31-36'' SEEVMK) towards an <scene name='Sandbox_Reserved_709/Nup50_bindingcas/1'>acidic surface</scene> on ARM10. Those electrostatic interactions are essential for the binding of Nup50. Indeed, replacing residues 41-46 by Ala makes the binding undetectable. Furthermore, this binding overlaps the CAS and the Ran binding sites, explaining why interaction between Nup50 and importin is crucial for building the export complex.
+The chain between the two binding segments is rich in acidic residues, and seems to work as a flexible linker between those two sites.