Sandbox Reserved 1713: Difference between revisions

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[[Image:Proteo_ALK-ALKAL_Monomer_White.png|400 px|right|thumb|Figure 2]]
[[Image:Proteo_ALK-ALKAL_Monomer_White.png|400 px|right|thumb|Figure 2]]
<scene name='90/904318/Binding_surface_with_residues/3'>interacting residues of ALK and ALKAL</scene>
<scene name='90/904318/Binding_surface_with_residues/3'>interacting residues of ALK and ALKAL</scene>
<scene name='90/904318/Alk-alkal_binding_surface/2'>ALK-ALKAL binding surface</scene>
<scene name='90/904318/Alkalbindingsurfacewmembrane/1'>Binding surface of ALKAL with the membrane</scene>
<scene name='90/904318/Alkalbindingsurfacewmembrane/1'>Binding surface of ALKAL with the membrane</scene>
<scene name='90/904318/Alkal1membraneinteraction/2'>ALKAL's residues that interact with membrane</scene>
<scene name='90/904318/Alkal1membraneinteraction/2'>ALKAL's residues that interact with membrane</scene>
===Conformational Change===
===Conformational Change===
The anaplastic lymphoma kinase activating ligand (ALKAL) binds to the <scene name='90/904318/Alk-alkal_binding_surface/2'>binding surface</scene> on the ALK at the TNFL domain. This induces a conformational change which allows for the PXL and the GlyR domains to hinge forward.<ref>DOI: 10.1038/s41586-021-04140-8</ref> (Figure 2) ALKAL-bound ALK is now ready to dimerize with another ALK-ALKAL complex
The anaplastic lymphoma kinase activating ligand (ALKAL) binds to the <scene name='90/904318/Alk-alkal_binding_surface/2'>binding surface</scene> on the ALK at the TNFL domain. This induces a conformational change which allows for the PXL and the GlyR domains to hinge forward.<ref>DOI: 10.1038/s41586-021-04140-8</ref> (Figure 2) ALK's TNFL has <scene name='90/904318/Binding_surface_with_residues/3'>residues</scene> E978, E974, E859, and Y966 that form salt bridges with R123, R133, R136, R140, and R117 on ALKAL that allow for activation, leading to dimerization of two ALK-ALKAL monomers.
===Movement across the membrane===
===Movement across the membrane===
The negatively charged phosphate groups on the cell membrane interact with the highly conserved positively charged residues on ALKAL ligand that face the membrane, which stabilizes the ligand to bind to ALK even better. <ref>DOI: 10.1038/s41586-021-04140-8</ref>
The negatively charged phosphate groups on the cell membrane interact with the highly conserved positively charged residues on ALKAL ligand that face the membrane, which stabilizes the ligand to bind to ALK even better. <ref>DOI: 10.1038/s41586-021-04140-8</ref>