Sandbox Reserved 1726: Difference between revisions

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OCA, Jaime Prilusky, Elizabeth A. Palumbo, Elizabeth Sutherlin, R. Jeremy Johnson

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 === Domains ===
 ==== Three Helix Bundle-like Domain ====
-The <scene name='90/904332/Thb-like_domain/1'>Three Helix Bundle-like Domain</scene> mainly has a structural function overall as it interacts with the TNF-like domain upon ligand binding. The THB-like domain's α-helix interacts with the helix α-1' and β strand A-1' on the TNF-like domain. This outermost region of the extracellular ligand-binding domain undergoes rigorous structural reorientation upon ligand binding. The THB-like is primarily involved in the dimerization motif of ALK, which dimerizes upon ligand binding. <ref name="Reshetnyak" />
+The <scene name='90/904332/Thb-like_domain/1'>Three Helix Bundle-like Domain</scene> mainly has a structural function as it interacts with the TNF-like domain upon ligand binding. The THB-like domain's α-helix interacts with the helix α-1' and β strand A-1' on the TNF-like domain. This outermost region of the extracellular ligand-binding domain undergoes rigorous structural reorientation upon ligand binding. The THB-like is primarily involved in the dimerization motif of ALK, which dimerizes upon ligand binding. <ref name="Reshetnyak" />
 ==== Poly-Glycine Domain ====
 [[Image:glycinehelicesorange.png|300 px|right|thumb|Figure 2. Rare Glycine helices on Anaplastic Lymphoma Kinase]]Located between the THB-like domain and the TNF-like domain, the <scene name='90/904331/Polyg_region1/4'>Poly-Glycine Region</scene> has an important structural role. The GlyR domain also has a rare and unique structure of left-handed glycine helices with hexagonal hydrogen bonding shown in Figure 2. These 14 glycine helices are unique to ALK's function among other tyrosine kinases, as these types of structures on the binding domain are not present. These helices are rigid structures, providing a strong anchor for the ligand binding site while the other domains undergo drastic conformational rearrangements.<ref name="Reshetnyak" />
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 ==== ALKAL1 ====
 <scene name='90/904331/Alkal1/5'>ALKAL1</scene> (Anaplastic Lymphoma Kinase Ligand 1) is a monomeric ligand of ALK, in addition to ALKAL2. Structurally, ALKAL1 and ALKAL2 contain an N-terminal variable region and a conversed C-terminal augmentor domain <ref name="Reshetnyak" />. However, in ALKAL1, this N-terminal variable region is shorter, and shares no similar sequences to ALKAL2. Nevertheless, ALKAL1 shares a 91% sequence similarity with ALKAL2. Both ligands include a three helix bundle domain in their structures, with an extended positively charged surface which is used in ligand binding <ref name="Reshetnyak" />.
-=== Dimerization of Anaplastic Lymphoma Kinase ===
+=== Dimerization of ALK ===
 After binding to one of its ligands, ALK undergoes <scene name='90/904331/Alk_full_dimerization/3'>ligand-induced dimerization</scene> <ref name="Huang">PMID:30400214</ref>. The [https://en.wikipedia.org/wiki/Dimer_(chemistry) dimerization] causes trans-phosphorylation of specific [https://en.wikipedia.org/wiki/Tyrosine tyrosine] residues which in turn amplifies the signal. It has been presumed that the [https://en.wikipedia.org/wiki/Phosphorylation_cascade phosphorylation cascade] activates ALK kinase activity <ref name="Huang" />.
 == Function ==