Sandbox Reserved 1713: Difference between revisions

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OCA, Jaime Prilusky, Andrew Peters, R. Jeremy Johnson, Hillary Kulavic

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 [[Image:Proteo_ALK-ALKAL_Monomer_White.png|400 px|right|thumb|Figure 2: ALK-ALKAL complex, showing the conformation change of ALK from the binding of ALKAL.]]
 ===Conformational Change===
-The anaplastic lymphoma kinase activating ligand (ALKAL) is a triple alpha-helix polypeptide structure that signals for a conformational change of ALK. It <scene name='90/904318/Alk-alkal_binding_surface/2'>binds</scene> to ALKr at the TNFL domain, which has important negatively charged <scene name='90/904318/Binding_surface_with_residues/3'>residues</scene> that form ionic bonds with positively charged residues on ALKAL. These bonds initiate the conformational change, as these residues can only come into close proximity with each other if the conformational change occurs. The PXL and GlyR domains hinge forward when the change is initiated<ref>DOI: 10.1038/s41586-021-04140-8</ref> (Figure 2). Glu978, Glu974, Glu859, and Tyr966 are the residues of ALKr that form these bonds with Arg123, Arg133, Arg136, Arg140, and Arg117 of ALKAL. Once the ALK-ALKAL complex is formed, the <scene name='90/904317/Dimer_full_colored/3'>dimerization</scene> of two ALK-ALKAL complexes occurs. There is not much known yet regarding how this dimerization is initiated, but one can assume that there are many strong bonds that facilitate this complex to form. This dimer of two ALK-ALKAL complexes is the active form of ALK, and it is now able to perform its main function.
+The anaplastic lymphoma kinase activating ligand (ALKAL) is a triple alpha-helix polypeptide structure that signals for a conformational change of ALK. It <scene name='90/904318/Dimer_full_colored/1'>binds</scene> to ALKr at the TNFL domain, which has important negatively charged residues that form <scene name='90/904318/Binding_surface_with_residues/3'>ionic bonds</scene> with positively charged residues on ALKAL. These bonds initiate the conformational change, as these residues can only come into close proximity with each other if the conformational change occurs. The PXL and GlyR domains hinge forward when the change is initiated<ref>DOI: 10.1038/s41586-021-04140-8</ref> (Figure 2). Glu978, Glu974, Glu859, and Tyr966 are the residues of ALKr that form these bonds with Arg123, Arg133, Arg136, Arg140, and Arg117 of ALKAL. Once the ALK-ALKAL complex is formed, the <scene name='90/904317/Dimer_full_colored/3'>dimerization</scene> of two ALK-ALKAL complexes occurs. The main driving force of the interaction between two ALK-ALKAL complexes that dimerize are hydrophobic interactions of the PXL loop of one ALKr with the other complex's ALKAL and TNFL domain of ALKr. This dimer of two ALK-ALKAL complexes is the active form of ALK, and it is now able to perform its main function of phosphorylation.
 ===Membrane Guidance of ALKAL to ALK===
 The negatively charged phosphate groups on the cell membrane interact with a highly conserved positively charged <scene name='90/904318/Alkalbindingsurfacewmembrane/1'>helix</scene> on ALKAL that faces the membrane. These <scene name='90/904318/Alkal1membraneinteraction/2'>residues that interact with the cell membrane</scene> guides ALKAL to ALK and correctly positions ALKAL for its <scene name='90/904318/Alk-alkal_binding_surface/4'>binding surface to face ALK's binding surface</scene>, which allows for a more favorable interaction. <ref>DOI: 10.1038/s41586-021-04140-8</ref>