Sandbox Reserved 1791: Difference between revisions

There are two <scene name='95/952719/Specific_residues/6'>lysine residues</scene> in the binding pocket of TSHR that are the main contributors to the binding of the antibodies. The concave structure of the binding pocket allows a <scene name='95/952719/Lock_and_key/8'>tight interaction</scene> with the antibodies. These antibodies make tight interactions with a lot of intermolecular forces at play. <scene name='95/952719/K---e_interaction/8'>LYS 58</scene> interacts with Glu 118 on the antibodies to make a [https://www.nature.com/articles/s41598-018-31935-z salt bridge interaction]. <scene name='95/952719/K---d_interaction/9'>LYS 209</scene> interacts with Asp 111 on the antibodies to make a salt bridge interaction. Specifically, the two residues make an ionic interaction. The interaction is not close enough to make a hydrogen bond. Instead, the interaction between the Lys residues with the Asp or Glu residues is a salt bridge interaction. This is the main bond that holds these two molecules together. When in the inactive form, LYS 209 does not interact with any residue but LYS 58 has interaction with Glu 118 and this interaction pulls the molecule into the bent position. The salt bridge interaction between Lys and Glu is very specific. Lys was mutated with Arg and was expected to make the same salt bride interaction with Glu, however it make a completely different interaction. This new interaction favors a gain of function towards [https://my.clevelandclinic.org/health/articles/22489-human-chorionic-gonadotropin hCG] <ref name="Guillaume">Smits G, Govaerts C, Nubourgh I, Pardo L, Vassart G, Costagliola S. Lysine 183 and glutamic acid 157 of the TSH receptor: two interacting residues with a key role in determining specificity toward TSH and human CG. Mol Endocrinol. 2002 Apr;16(4):722-35. doi: 10.1210/mend.16.4.0815. PMID: 11923469. [DOI: 10.1210/mend.16.4.0815 https://pubmed.ncbi.nlm.nih.gov/11923469/]</ref>.