Sandbox 27: Difference between revisions
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* '''A C-terminal intracellular domain''' | * '''A C-terminal intracellular domain''' | ||
Full information about the LRD domain from : [http://www.hotthyroidology.com/editorial_175.html Hot Thyroidology Journal] <ref> B R Smith, J Sanders, J Furmaniak, The TSH receptor – a new cristal structure, Hot Thyroidology Journal, article n°175 | Full information about the LRD domain from : [http://www.hotthyroidology.com/editorial_175.html Hot Thyroidology Journal] <ref> B R Smith, J Sanders, J Furmaniak, The TSH receptor – a new cristal structure, Hot Thyroidology Journal, article n°175</ref> | ||
One of models for the receptor’s activation explains that interactions between ectodomain and extracellular loops would inhibit the activity of serpentine domain in the absence of stimulation. But when TSH is binding to LRD, the ectodomain would have a change of conformation which activates the transduction of signal. <ref> V Vlaeminck-Guillem, G Vassart et S Costagliola, Un modèle d’activation du récepteur de la TSH / A THS receptor activation model, M/S : médecine sciences, vol. 18, n° 12, 2002, p. 1184-1186. </ref> | One of models for the receptor’s activation explains that interactions between ectodomain and extracellular loops would inhibit the activity of serpentine domain in the absence of stimulation. But when TSH is binding to LRD, the ectodomain would have a change of conformation which activates the transduction of signal. <ref> V Vlaeminck-Guillem, G Vassart et S Costagliola, Un modèle d’activation du récepteur de la TSH / A THS receptor activation model, M/S : médecine sciences, vol. 18, n° 12, 2002, p. 1184-1186.[[http://www.erudit.org/revue/MS/2002/v18/n12/000588ar.pdf]] </ref> | ||
== Structure of the complexe TSHR – M22 == | == Structure of the complexe TSHR – M22 == | ||
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M22 binds to the concave surface of the LRD domain (only a fragment of this domain is represented on the pdb structure: residues 22 to 260 of TSHR) | M22 binds to the concave surface of the LRD domain (only a fragment of this domain is represented on the pdb structure: residues 22 to 260 of TSHR) | ||
The binding results of several interactions between TSHR and M22, most of them are hydrogen bonds and salt bridges. The <scene name='Sandbox_27/Chaine_b/3'>heavy chain</scene> (HC, or Chain B) of M22 has more interactions with the <scene name='Sandbox_27/Chaine_c/1'>LRD</scene> than has the <scene name='Sandbox_27/Chaine_a/2'>light chain</scene> (LC, or Chain A), respectively 14 and 8 interactions. <ref> J. Sanders and co Crystal, Structure of the TSH Receptor in Complex with a Thyroid-Stimulating Autoantibody, THYROID Volume 17, Number 5, 2007 PMID:17542669 </ref> | The binding results of several interactions between TSHR and M22, most of them are hydrogen bonds and salt bridges. The <scene name='Sandbox_27/Chaine_b/3'>heavy chain</scene> (HC, or Chain B) of M22 has more interactions with the <scene name='Sandbox_27/Chaine_c/1'>LRD</scene> than has the <scene name='Sandbox_27/Chaine_a/2'>light chain</scene> (LC, or Chain A), respectively 14 and 8 interactions. <ref> J. Sanders and co Crystal, Structure of the TSH Receptor in Complex with a Thyroid-Stimulating Autoantibody, THYROID Volume 17, Number 5, 2007 [http://www.ncbi.nlm.nih.gov/pubmed/19221175 PMID:17542669] </ref> | ||
The binding of M22 to the LRD must induce changes in the receptor conformation, which cause signal induction, but the nature of these changes are not currently known. Indeed no movement of the atoms of M22 is observed after its binding to the receptor. This conformational change may occur also with TSH binding. | The binding of M22 to the LRD must induce changes in the receptor conformation, which cause signal induction, but the nature of these changes are not currently known. Indeed no movement of the atoms of M22 is observed after its binding to the receptor. This conformational change may occur also with TSH binding. | ||
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Other 3D structure of complexes between TSHR and autoantibodies from pdb: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2XWT 2xwt] | |||
== Diseases == | == Diseases == | ||