Sandbox Reserved 813: Difference between revisions
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== Linker== | == Linker== | ||
The linker tethers the two POU subdomains and is hypervariable in both sequence and length. Thus the linker in Oct-4 contrarly to the linker of the other member of the POU family like Oct-1 [http://en.wikipedia.org/wiki/POU2F1], is an 17 amino acid “alpha”-helix and is exposed to the protein surface. The Oct4 linker functions as a '''protein-protein interaction''' interface and plays a highly important role during '''reprogramming'''. This alpha 5 helix interacts with helices alpha 2 and alpha 4 of POU s mostly by Van der Waals interaction, except for the hydrogen bond between<scene name='56/568011/Liaison_25-81/1'>Tyr 25 of POUs and Gln 81</scene> of the linker. The interaction between Val 36 of POUs and the the carboxy-terminal of the helix alpha 5 of the linker plays an important role. In all known Oct-4 sequences <scene name='56/568011/Asn79_and_leu80/1'>Asn79 and Leu80 </scene> are invariant but not conserved in other members of Oct family. Mutation in the linker of GLn81 by an Arg leads to a complete loss-of-function phenotype. Likewise mutation of Leu80 by an Ala abolished biological activity. It is deduces that this mutation disturb an interaction surface with yet unknown additional factors. Overall mutation of the linker of the protein lead<scene name='56/568011/Asn76_asn_77_asn_79/1'>residues exposed to the surface</scene>(Asn76, Asn 77, Asn 79) to significantly fewer function. The integrity of the linker is essential for successful reprogramming. | The linker tethers the two POU subdomains and is hypervariable in both sequence and length. Thus the linker in Oct-4 contrarly to the linker of the other member of the POU family like Oct-1 [http://en.wikipedia.org/wiki/POU2F1], is an 17 amino acid “alpha”-helix and is exposed to the protein surface. The Oct4 linker functions as a '''protein-protein interaction''' interface and plays a highly important role during '''reprogramming'''. This alpha 5 helix interacts with helices alpha 2 and alpha 4 of POU s mostly by Van der Waals interaction, except for the hydrogen bond between<scene name='56/568011/Liaison_25-81/1'>Tyr 25 of POUs and Gln 81</scene> of the linker. The interaction between Val 36 of POUs and the the carboxy-terminal of the helix alpha 5 of the linker plays an important role. In all known Oct-4 sequences <scene name='56/568011/Asn79_and_leu80/1'>Asn79 and Leu80 </scene> are invariant but not conserved in other members of Oct family. Mutation in the linker of GLn81 by an Arg leads to a complete loss-of-function phenotype. Likewise mutation of Leu80 by an Ala abolished biological activity. It is deduces that this mutation disturb an interaction surface with yet unknown additional factors. Overall mutation of the linker of the protein lead <scene name='56/568011/Asn76_asn_77_asn_79/1'>residues exposed to the surface</scene>(Asn76, Asn 77, Asn 79) to significantly fewer function. The integrity of the linker is essential for successful reprogramming. | ||
On the figure n°4, we can see the surrounding of the linker. There are different hydrogen bonds to save the tridimentional structure of OCT-4: the first hydrogen bond is located between <scene name='56/568011/Hydrogen_bond_between_33-_70/1'>the tyrosine 33 and the | On the figure n°4, we can see the surrounding of the linker. There are different hydrogen bonds to save the tridimentional structure of OCT-4: the first hydrogen bond is located between <scene name='56/568011/Hydrogen_bond_between_33-_70/1'>the tyrosine 33 and the tryptophane 70</scene>. | ||
The linker recruits key partners to the Oct 4 target genes and change in the sequence of the linker lead to the loss of Oct 4' reprogramming activity. | The linker recruits key partners to the Oct 4 target genes and change in the sequence of the linker lead to the loss of Oct-4' reprogramming activity. | ||