Sandbox Reserved 1712: Difference between revisions
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The domains that aren't shown in Figure 2 but are shown in the domain map (Figure 1) also make up the monomer. The heparin binding domains (HBDs), are at the N-terminal end of the monomer. Heparin has been found to be a possible activating ligand of ALK.<ref>DOI: 10.1126/scisignal.2005916</ref> The transmembrane domain (TMH) contains the residues of ALK that are located within the membrane. The kinase domain is the intracellular portion of ALK that contains the Tyr residues which are auto-phosphorylated when ALK is activated, initiating a signaling cascade. <ref>DOI: 10.1038/s41586-021-04141-7</ref> | The domains that aren't shown in Figure 2 but are shown in the domain map (Figure 1) also make up the monomer. The heparin binding domains (HBDs), are at the N-terminal end of the monomer. Heparin has been found to be a possible activating ligand of ALK.<ref>DOI: 10.1126/scisignal.2005916</ref> The transmembrane domain (TMH) contains the residues of ALK that are located within the membrane. The kinase domain is the intracellular portion of ALK that contains the Tyr residues which are auto-phosphorylated when ALK is activated, initiating a signaling cascade. <ref>DOI: 10.1038/s41586-021-04141-7</ref> | ||
[[Image:Conformational change 2D.png| | [[Image:Conformational change 2D.png|600 px|center|thumb|Figure 3: ALK-ALKAL complex, showing the conformation change of ALK from the binding of ALKAL. [https://www.rcsb.org/structure/7N00 PDB: 7N00]]] | ||
===Conformational Change=== | ===Conformational Change=== | ||
The anaplastic lymphoma kinase activating ligand (ALKAL) binds to the <scene name='90/904317/Alk-alkal_binding_surface/1'>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 3) ALK's TNFL has <scene name='90/904317/Binding_surface_with_residues/1'>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 <scene name='90/904317/Dimer_full_colored/5'>dimerization</scene> of two ALK-ALKAL monomers. | The anaplastic lymphoma kinase activating ligand (ALKAL) binds to the <scene name='90/904317/Alk-alkal_binding_surface/1'>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 3) ALK's TNFL has <scene name='90/904317/Binding_surface_with_residues/1'>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 <scene name='90/904317/Dimer_full_colored/5'>dimerization</scene> of two ALK-ALKAL monomers. | ||
