Sandbox Reserved 1791: Difference between revisions
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== Specific Residues and Interactions== | == Specific Residues and Interactions== | ||
On the concave surface of the LRRD two <scene name='95/952719/Specific_residues/6'>lysine residues</scene> 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 antibodies. Specifically, <scene name='95/952719/K---e_interaction/8'>LYS 58</scene> interacts with Glu 118 and <scene name='95/952719/K---d_interaction/9'>LYS 209</scene> interacts with Asp 111 on K1 and M22 antibodies to make a [https://www.nature.com/articles/s41598-018-31935-z salt bridge 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 [https://www.nature.com/articles/s41598-018-31935-z salt bridge interaction] because the distance between the residues is greater than 2Å. When in the inactive form, LYS 209 interaction is absent but LYS 58 interaction with Glu 118 is present. These salt bridge interactions are highly specific as mutation of Lys209 to Arg induced a different interaction. This new interaction widens the selectivity of TSHR, allowing it to bind to other hormones | On the concave surface of the LRRD two <scene name='95/952719/Specific_residues/6'>lysine residues</scene> 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 antibodies. Specifically, <scene name='95/952719/K---e_interaction/8'>LYS 58</scene> interacts with Glu 118 and <scene name='95/952719/K---d_interaction/9'>LYS 209</scene> interacts with Asp 111 on K1 and M22 antibodies to make a [https://www.nature.com/articles/s41598-018-31935-z salt bridge 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 [https://www.nature.com/articles/s41598-018-31935-z salt bridge interaction] because the distance between the residues is greater than 2Å. When in the inactive form, LYS 209 interaction is absent but LYS 58 interaction with Glu 118 is present. These salt bridge interactions are highly specific as mutation of Lys209 to Arg induced a different interaction. This new interaction widens the selectivity of TSHR, allowing it to bind to other hormones<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>. | ||
== Biological Relevance == | == Biological Relevance == | ||
