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

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 =Anaplastic Lymphoma Kinase=
 ==Background==
-The anaplastic lymphoma kinase (ALK) was first discovered in 1994 as a tyrosine [https://en.wikipedia.org/wiki/Kinase kinase] in anaplastic large-cell lymphoma (ALCL) cells.<ref>DOI: 10.3390/ijms19113448</ref> The specific type of tyrosine kinase ALK is classified as is a [https://en.wikipedia.org/wiki/Receptor_tyrosine_kinase receptor tyrosine kinase] (RTK) and like other RTKs, it's an integral protein with extracellular and intracellular domains and is involved in transmembrane signaling and communication within the cell. ALK is commonly expressed in the development of the nervous system. Anaplastic lymphoma kinase receptor (ALKr) is the extracellular portion of the RTK that includes a binding surface for a ligand to bind. When the ALK activating ligand (ALKAL) binds to ALKr, this causes a conformational change of ALK, allowing the intracellular kinase domain of ALK to phosphorylate a tyrosine residue on a downstream enzyme, which will activate this enzyme and activate a signaling cascade. Abnormal forms of ALK are closely related to the formation of several cancers. <ref>DOI: 10.3390/ijms19113448</ref>
+The anaplastic lymphoma kinase (ALK) was first discovered in 1994 as a tyrosine [https://en.wikipedia.org/wiki/Kinase kinase] in anaplastic large-cell lymphoma (ALCL) cells.<ref>DOI: 10.3390/ijms19113448</ref> The specific type of tyrosine kinase ALK is classified as is a [https://en.wikipedia.org/wiki/Receptor_tyrosine_kinase receptor tyrosine kinase] (RTK) and like other RTKs, it's an integral protein with extracellular and intracellular domains and is involved in transmembrane signaling and communication within the cell. ALK is commonly expressed in the development of the nervous system. Anaplastic lymphoma kinase receptor (ALKr) is the extracellular portion of the RTK that includes a binding surface for a ligand to bind. When the ALK activating ligand (ALKAL) binds to ALKr, this causes a conformational change of ALK, allowing two ALK-ALKAL complexes to interact with each other, which will then allow intracellular kinase domain of ALK to phosphorylate a tyrosine residue on a downstream enzyme, which will activate this enzyme and activate a signaling cascade. Abnormal forms of ALK are closely related to the formation of several cancers. <ref>DOI: 10.3390/ijms19113448</ref>
 <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
 == Structure & Function ==
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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) 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 <scene name='90/904317/Dimer_full_colored/3'>dimerization</scene> of two ALK-ALKAL monomers.
+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 binding surface to face ALK's binding surface, which allows for a more favorable interaction. <ref>DOI: 10.1038/s41586-021-04140-8</ref>
+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>
 ===Role of Activated ALK===
 Once the ALKAL binds with ALK and dimerizes with another ALK-ALKAL complex, this activated conformation also initiates a conformational change of the intracellular kinase domain of ALK. This causes an autophosphorylation of several tyrosine residues of this domain, activating a signaling cascade with its kinase activity.