Sandbox Reserved 1712: Difference between revisions

Jump to navigation Jump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 8: Line 8:
[[Image:Updated schematic.png|700 px|center|thumb|Figure 1: Anaplastic Lymphoma Kinase and its domains.]]
[[Image:Updated schematic.png|700 px|center|thumb|Figure 1: Anaplastic Lymphoma Kinase and its domains.]]


The region from NTR (N-terminal region) to the MAM is the Heparin Binding Domain. The TNFL through the PXL (polyglycine extension loop) are the extracellular domains and the EGF is the domain that binds to the TMH (transmembrane region) region in the membrane. The kinase domain is the intracellular portion of the ALK and the structure has not been discovered. The only structures that have been fully discovered are in color (Figure 1). The growth factor-like domain (EGF) connects the extracellular domains to the transmembrane domain (cyan). The tumor necrosis factor-like domain (TNFL) has a beta-sandwich structure that provides important residues that act as the binding surface for the ligand (orange). The glycine-rich domain (GlyR) contains 14 rare polyglycine helices that are hydrogen-bound to each other (green). The extracellular portion of ALK has an inactive state <scene name='90/904317/Glycinerichmonomer/6'>monomer</scene>, and upon ligand binding, ALK transitions to an active <scene name='90/904317/Dimer_full_colored/7'>dimerized</scene> state. The monomer has many different domains (Figure 1). The <scene name='90/904317/Glycinerichdomain/1'>hexagonal orientation</scene> of these rare helices create a rigid structure that is important for ALK function. The <scene name='90/904317/Glycinerichmonomer/8'>GlyR</scene> domain functions as a scaffold to anchor the ligand-binding site on the TNF-like domain and the overall dimerization of the three-helix bundle. The polyglycine extension loop (PXL) connects two of these polyglycine helices (pink).
ALKr has many different domains that are important to its function (Figure 1). 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. The EGF (cyan) is the domain that binds to the TMH (transmembrane region), connecting the extracellular portion of ALK to the intracellular kinase domain. The only structures that have been fully discovered are in color (Figure 1). TNFL (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/1'>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 PXL (pink) connects two of these polyglycine helices, and it also plays a role in forming important interactions of the dimerized activated state of ALKr. The extracellular portion of ALK has an inactive state <scene name='90/904317/Glycinerichmonomer/6'>monomer</scene>, and upon ligand binding, ALK transitions to an active <scene name='90/904317/Dimer_full_colored/7'>dimerized</scene> state.


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>

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA, Jaime Prilusky, Hillary Kulavic, Andrew Peters, R. Jeremy Johnson
Retrieved from "https://proteopedia.openfox.io/w/Sandbox_Reserved_1712"