RA Mediated T-reg Differentiation: Difference between revisions
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=== RARα-RXRα Ligand Interactions === | === RARα-RXRα Ligand Interactions === | ||
Upon binding of the ligand ATRA in the cytoplasm, RARα and RXRα form a heterodimer | Upon binding of the ligand ATRA in the cytoplasm, RARα and RXRα form a heterodimer and alter the C-terminals on domain H12 of both subunits in a manner that allows them to change the conformation of their DNA binding domains. The two proteins have 29% identity in their <scene name='RA_Mediated_T-reg_Differentiaition/Ligand_binding_pockets/1'>LBD</scene>. | ||
For the ligand used in RARα crystallization, BMS614, 21 primarily hydrophobic residues form the <scene name='RA_Mediated_T-reg_Differentiaition/Rar-ligand_binding_pocket/1'>RAR-alpha ligand binding pocket</scene>. BMS614 is not the natural ligand for this molecule, but acts as an more stable agonist for crystallization. The largest difference between BMS614 and ATRA upon binding to the pocket are at Ile 412, where BMS614 pushes much closer to the amino acid than ATRA does. | For the ligand used in RARα crystallization, BMS614, 21 primarily hydrophobic residues form the <scene name='RA_Mediated_T-reg_Differentiaition/Rar-ligand_binding_pocket/1'>RAR-alpha ligand binding pocket</scene>. BMS614 is not the natural ligand for this molecule, but acts as an more stable agonist for crystallization. The largest difference between BMS614 and ATRA upon binding to the pocket are at Ile 412, where BMS614 pushes much closer to the amino acid than ATRA does. Residues that form the binding pocket are found on H1, H3, H5, H11, L6-7, and L11-12 on RARα. | ||
The <scene name='RA_Mediated_T-reg_Differentiaition/Rar-ligand_binding_pocket2/1'>major differences</scene> between RARα, RARβ and RARγ are present in this area: | The <scene name='RA_Mediated_T-reg_Differentiaition/Rar-ligand_binding_pocket2/1'>major differences</scene> between RARα, RARβ and RARγ are present in this area: | ||
Residue 270: α:Ile β:Ile γ:Met; Residue 232: α:Ser β:Ala γ:Ala; Residue 395: α:Val β:Val γ:Ala | Residue 270: α:Ile β:Ile γ:Met; Residue 232: α:Ser β:Ala γ:Ala; Residue 395: α:Val β:Val γ:Ala | ||
The <scene name='RA_Mediated_T-reg_Differentiaition/Rxr-ligand_binding_pocket/1'>RXR-alpha binding pocket</scene> is comprised of 16 primarily hydrophobic residues. The ligand used in the crystal, Oleic Acid, is similar to RA, and RA is capable of binding to the RXRα pocket.<ref> PMID: 10882070 </ref> | The <scene name='RA_Mediated_T-reg_Differentiaition/Rxr-ligand_binding_pocket/1'>RXR-alpha binding pocket</scene> is comprised of 16 primarily hydrophobic residues, found on the H3, H5, H7, H11, and L11-12 domains. The ligand used in the crystal, Oleic Acid, is similar to RA, and RA is capable of binding to the RXRα pocket.<ref> PMID: 10882070 </ref> | ||