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M22 is a thyroid stimulating human monoclonal antibody prepared using lymphocytes from a patient with Graves’ disease. It is an antibody to the TSHR. It mimics closely the binding of TSH on its receptor, so it stimulates the receptor and inhibits the binding of TSH to give rise to full activation of receptor mediated signal transduction.
M22 is a thyroid stimulating human monoclonal antibody prepared using lymphocytes from a patient with Graves’ disease. It is an antibody to the TSHR. It mimics closely the binding of TSH on its receptor, so it stimulates the receptor and inhibits the binding of TSH to give rise to full activation of receptor mediated signal transduction.
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== Signalling pathway ==
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== Structure of the TSH Receptor ==
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This receptor is evolutionary classified as rhodopsin-like receptors of family A. It is consisted of 3 different domains:
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* An extracellular domain consisting of ten leucine-rich repeats (leucine rich domain: LRD), with a N-terminal tail linked by S-S bonds. This ectodomain is responsible for the high affinity and selective binding of the corresponding hormones.
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* A N-terminal tail: it contains 4 half-cystines (i.e. one of the two disulphide-bonded cysteines) and is disulphide bonded to the first of ten repeats of the LRD

Revision as of 12:15, 9 December 2011

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Contents

TSH Receptor in complex with the thyroid-stimulating autoantibody M22

The thyrotropin receptor (or TSH receptor or TSHR) is a member of the G protein-coupled receptor superfamily of integral membrane proteins and is coupled to the Gs protein. It is on the surface of thyroid follicular cells. Once stimulated by TSH (Thyroid-Stimulating Hormone), THSR activates the production of thyroid hormones: thyroxine (T4) and triiodothyronine (T3).


TSH and M22

TSH is a hormone also known as "thyrotropin". It is a member of the glycoprotein family (like LH, FSH or hCG). TSH regulates growth and function of thyroid follicular cells, and the gonadotropins LH/CG and FSH play an important role in human reproduction. Therefore, this class of receptors is central to medical, pharmaceutical, and biological research.

The studies on the structure of TSH receptor are based upon its binding to an antibody called M22. Crystals suitable for X-Ray diffraction analysis were obtained and the structure solved at 2.55 A resolution.

M22 is a thyroid stimulating human monoclonal antibody prepared using lymphocytes from a patient with Graves’ disease. It is an antibody to the TSHR. It mimics closely the binding of TSH on its receptor, so it stimulates the receptor and inhibits the binding of TSH to give rise to full activation of receptor mediated signal transduction.

Signalling pathway

Structure of the TSH Receptor

This receptor is evolutionary classified as rhodopsin-like receptors of family A. It is consisted of 3 different domains:

  • An extracellular domain consisting of ten leucine-rich repeats (leucine rich domain: LRD), with a N-terminal tail linked by S-S bonds. This ectodomain is responsible for the high affinity and selective binding of the corresponding hormones.
  • A N-terminal tail: it contains 4 half-cystines (i.e. one of the two disulphide-bonded cysteines) and is disulphide bonded to the first of ten repeats of the LRD
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