Sandbox Reserved 1712: Difference between revisions

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

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 [[Image:Updated schematic.png|700 px|center|thumb|Figure 1: Anaplastic Lymphoma Kinase and its domains.]]
-ALKr is in its inactive state as a <scene name='90/904317/Glycinerichmonomer/6'>monomer</scene> and has many different domains (Figure 1) that are important to the formation of the <scene name='90/904317/Dimer_full_colored/12'>dimerized</scene> active state, leading to ALK's main function. The tumor necrosis factor-like domian (TNFL), glycine-rich domain (GlyR), polyglycine extension loop (PXL), and growth factor-like domain (EGF) are the main domains of ALKr, and the only domains whose structures have been fully discovered are in color (Figure 1). The <scene name='90/904317/Glycinerichmonomer/11'>EGF</scene> (cyan) is the domain that binds to the TMH (transmembrane region), connecting the extracellular portion of ALK to the intracellular kinase domain.  <scene name='90/904317/Glycinerichmonomer/10'>TNFL</scene> (orange) has a beta-sandwich structure that provides important residues that act as the binding surface for the ligand. <scene name='90/904317/Glycinerichmonomer/8'>GlyR</scene> (green) contains 14 rare polyglycine helices that are hydrogen-bound to each other. The <scene name='90/904317/Glycinerichdomain/4'>hexagonal orientation</scene> of these rare helices create a rigid structure which allows it to function as a scaffold to anchor the ligand-binding site on the TNF-like domain while bound to the ligand. The numberous hydrogen bonds are what create this <scene name='90/904317/Glycinerichdomain/3'>formation</scene> of the helices and the rigidity of the structure. The <scene name='90/904317/Glycinerichmonomer/9'>PXL</scene> (pink) connects two of these polyglycine helices, and it also plays a role in forming important interactions of the dimerized activated state of ALKr.
+ALKr is in its inactive state as a <scene name='90/904317/Glycinerichmonomer/12'>monomer</scene> and has many different domains (Figure 1) that are important to the formation of the <scene name='90/904317/Dimer_full_colored/12'>dimerized</scene> active state, leading to ALK's main function. The tumor necrosis factor-like domian (TNFL), glycine-rich domain (GlyR), polyglycine extension loop (PXL), and growth factor-like domain (EGF) are the main domains of ALKr, and the only domains whose structures have been fully discovered are in color (Figure 1). The <scene name='90/904317/Glycinerichmonomer/11'>EGF</scene> (cyan) is the domain that binds to the TMH (transmembrane region), connecting the extracellular portion of ALK to the intracellular kinase domain.  <scene name='90/904317/Glycinerichmonomer/10'>TNFL</scene> (orange) has a beta-sandwich structure that provides important residues that act as the binding surface for the ligand. <scene name='90/904317/Glycinerichmonomer/8'>GlyR</scene> (green) contains 14 rare polyglycine helices that are hydrogen-bound to each other. The <scene name='90/904317/Glycinerichdomain/4'>hexagonal orientation</scene> of these rare helices create a rigid structure which allows it to function as a scaffold to anchor the ligand-binding site on the TNF-like domain while bound to the ligand. The numberous hydrogen bonds are what create this <scene name='90/904317/Glycinerichdomain/3'>formation</scene> of the helices and the rigidity of the structure. The <scene name='90/904317/Glycinerichmonomer/9'>PXL</scene> (pink) connects two of these polyglycine helices, and it also plays a role in forming important interactions of the dimerized activated state of ALKr.
 Additional domains are present in ALK monomers (Figure 1), but their structures are not currently known. The heparin binding domains (HBDs), are at the N-terminal end of the monomer. Heparin is a likely activating ligand of ALK.<ref>DOI: 10.1126/scisignal.2005916</ref> The transmembrane domain (TMH) contains the membrane spanning portion of ALK that transmits extracellular ligand binding into an intracellular signal. 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:Con chang 2D.png|600 px|center|thumb|Figure 2: ALK-ALKAL complex, showing the conformation change of ALK from the binding of ALKAL. [https://www.rcsb.org/structure/7N00 PDB: 7N00]]]