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Antoine Lambert: PDBID and PDB link

Antoine Lambert — Thu, 20 Jan 2022 15:36:06 GMT

PDBID and PDB link

←Older revision		Revision as of 15:36, 20 January 2022
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	[https://en.wikipedia.org/wiki/Thyroglobulin Human thyroglobulin (TG)] is a precursor of two [https://en.wikipedia.org/wiki/Thyroid_hormones thyroid hormones] (TH): tetraiodothyronine or [[thyroxine]] (T4) and [[triiodothyronine (T3)]], essential for '''growth''', '''development''' and the '''control of metabolism'''. Its structure is essential for the diagnosis, treatment and monitoring of thyroid-related diseases.		[https://en.wikipedia.org/wiki/Thyroglobulin Human thyroglobulin (TG)] is a precursor of two [https://en.wikipedia.org/wiki/Thyroid_hormones thyroid hormones] (TH): tetraiodothyronine or [[thyroxine]] (T4) and [[triiodothyronine (T3)]], essential for '''growth''', '''development''' and the '''control of metabolism'''. Its structure is essential for the diagnosis, treatment and monitoring of thyroid-related diseases.

		+	'''PDBID''': 6scj.
		+
		+	[https://www.rcsb.org/sequence/6SCJ/ See the complete sequence.]

	== Composition and 3D structure <ref>DOI 32025030</ref> ==		== Composition and 3D structure <ref>DOI 32025030</ref> ==

Antoine Lambert at 15:08, 18 January 2022

Antoine Lambert — Tue, 18 Jan 2022 15:08:14 GMT

←Older revision		Revision as of 15:08, 18 January 2022
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	=== Expression of the TG gene===		=== Expression of the TG gene===
-	In humans, TG is coded by a large gene roughly '''300 kb long''', located on chromosome 8. The number of exons has been estimated to be around 48, each of which is separated by introns varying in size up to 64 kb. TG gene ~~expresion~~ is controlled positively by '''thyro-tropin (TSH)''' through the modulation of the intra-cellular levels of '''cyclic adenosine monophosphate (cAMP)''' via its receptor (TSHr) located at the basal membrane of the cell.<ref>PMID: 11581009</ref>	+	In humans, TG is coded by a large gene roughly '''300 kb long''', located on chromosome 8. The number of exons has been estimated to be around 48, each of which is separated by introns varying in size up to 64 kb. TG gene expression is controlled positively by '''thyro-tropin (TSH)''' through the modulation of the intra-cellular levels of '''cyclic adenosine monophosphate (cAMP)''' via its receptor (TSHr) located at the basal membrane of the cell.<ref>PMID: 11581009</ref>

	=== Post-translational modifications ===		=== Post-translational modifications ===

Antoine Lambert at 16:11, 17 January 2022

Antoine Lambert — Mon, 17 Jan 2022 16:11:14 GMT

←Older revision		Revision as of 16:11, 17 January 2022
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	== Interest in the medical field<ref>DOI 6814409</ref><ref>DOI 29984794</ref><ref name="jeso"/> ==		== Interest in the medical field<ref>DOI 6814409</ref><ref>DOI 29984794</ref><ref name="jeso"/> ==
-	=== Modification of the TG quantity related to the ~~desease~~ ===	+	=== Modification of the TG quantity related to the disease ===
	A healthy subject has between '''5 and 25 µg of TG per liter''' of blood.<ref>DOI 5773064</ref> In case of thyroid dysfunction, this level may increase or decrease. For example, it decreases in the case of congenital athyreosis (insufficiency of the thyroid gland) or prior to a miscarriage due to the presence of anti-TG antibodies, but increases in the case of cancer, thyroiditis, inflammation of the thyroid or autoimmune thyroid diseases '''AITD''' <ref>DOI 24147207</ref>(Grave's disease, Hashimoto's thyroiditis).<ref>DOI 11788684</ref><ref>DOI 17614775</ref>		A healthy subject has between '''5 and 25 µg of TG per liter''' of blood.<ref>DOI 5773064</ref> In case of thyroid dysfunction, this level may increase or decrease. For example, it decreases in the case of congenital athyreosis (insufficiency of the thyroid gland) or prior to a miscarriage due to the presence of anti-TG antibodies, but increases in the case of cancer, thyroiditis, inflammation of the thyroid or autoimmune thyroid diseases '''AITD''' <ref>DOI 24147207</ref>(Grave's disease, Hashimoto's thyroiditis).<ref>DOI 11788684</ref><ref>DOI 17614775</ref>

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	The variation of the quantity of TG can thus be as much a cause as a consequence of disease.<ref>DOI 17201802</ref>		The variation of the quantity of TG can thus be as much a cause as a consequence of disease.<ref>DOI 17201802</ref>

-	=== Use of TG to treat ~~deseases~~ ===	+	=== Use of TG to treat diseases ===
	A classic '''TSH-stimulated''' <scene name='86/868183/Tg/3'>TG</scene> measurement or ultrasensitive <scene name='86/868183/Tg/4'>TG</scene> measurement allows to control its rate in a more or less sensitive way and therefore to detect a disease like those mentioned above, to ensure the effectiveness of a treatment and the absence of recurrence and to avoid		A classic '''TSH-stimulated''' <scene name='86/868183/Tg/3'>TG</scene> measurement or ultrasensitive <scene name='86/868183/Tg/4'>TG</scene> measurement allows to control its rate in a more or less sensitive way and therefore to detect a disease like those mentioned above, to ensure the effectiveness of a treatment and the absence of recurrence and to avoid
	miscarriages.<ref>DOI 3681445</ref>		miscarriages.<ref>DOI 3681445</ref>

Antoine Lambert at 16:09, 17 January 2022

Antoine Lambert — Mon, 17 Jan 2022 16:09:45 GMT

←Older revision		Revision as of 16:09, 17 January 2022
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	=== Use of TG to treat deseases ===		=== Use of TG to treat deseases ===
-	A classic '''TSH-stimulated''' <scene name='86/868183/Tg/3'>TG</scene> measurement or ultrasensitive <scene name='86/868183/Tg/3'>TG</scene> measurement allows to control its rate in a more or less sensitive way and therefore to detect a disease like those mentioned above, to ensure the effectiveness of a treatment and the absence of recurrence and to avoid	+	A classic '''TSH-stimulated''' <scene name='86/868183/Tg/3'>TG</scene> measurement or ultrasensitive <scene name='86/868183/Tg/4'>TG</scene> measurement allows to control its rate in a more or less sensitive way and therefore to detect a disease like those mentioned above, to ensure the effectiveness of a treatment and the absence of recurrence and to avoid
	miscarriages.<ref>DOI 3681445</ref>		miscarriages.<ref>DOI 3681445</ref>
	Since serum <scene name='86/868183/Tg/3'>TG</scene> levels are correlated with the volume of thyroid tissue, we can also estimate the mass of thyroid tissue to detect '''hyperthyroidism''', a disease related to an enlarged thyroid or, conversely, '''hypothyroidism'''.		Since serum <scene name='86/868183/Tg/3'>TG</scene> levels are correlated with the volume of thyroid tissue, we can also estimate the mass of thyroid tissue to detect '''hyperthyroidism''', a disease related to an enlarged thyroid or, conversely, '''hypothyroidism'''.

Antoine Lambert at 16:05, 17 January 2022

Antoine Lambert — Mon, 17 Jan 2022 16:05:46 GMT

←Older revision		Revision as of 16:05, 17 January 2022
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	=== Post-translational modifications ===		=== Post-translational modifications ===
-	TG also undergoes N-glycosylations in the [https://en.wikipedia.org/wiki/Endoplasmic_reticulum/ endoplasmic reticulum] at <scene name='86/868183/Glycosylation_sites/1'>17 glycosylation sites</scene>, so that 10% of its molecular weight is carbohydrate. TG also undergoes maturation steps in this organelle, where it acquires dilsufide-bonds. These modifications enhance its stability and solubility. Indeed, the two monomers are linked not by covalent interactions but via numerous interactions allowed by these N-glycosylations.	+	TG also undergoes N-glycosylations in the [https://en.wikipedia.org/wiki/Endoplasmic_reticulum endoplasmic reticulum] at <scene name='86/868183/Glycosylation_sites/1'>17 glycosylation sites</scene>, so that 10% of its molecular weight is carbohydrate. TG also undergoes maturation steps in this organelle, where it acquires dilsufide-bonds. These modifications enhance its stability and solubility. Indeed, the two monomers are linked not by covalent interactions but via numerous interactions allowed by these N-glycosylations.

	=== Folding ===		=== Folding ===
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	Since serum <scene name='86/868183/Tg/3'>TG</scene> levels are correlated with the volume of thyroid tissue, we can also estimate the mass of thyroid tissue to detect '''hyperthyroidism''', a disease related to an enlarged thyroid or, conversely, '''hypothyroidism'''.		Since serum <scene name='86/868183/Tg/3'>TG</scene> levels are correlated with the volume of thyroid tissue, we can also estimate the mass of thyroid tissue to detect '''hyperthyroidism''', a disease related to an enlarged thyroid or, conversely, '''hypothyroidism'''.

-	For example, [https://en.wikipedia.org/wiki/Thyroidectomy/ thyroidectomy] and a iodine-131 therapy can be performed to cure thyroid cancer with an 80% chance. Following removal and iodine-131 therapy, thyroglobulin is this time produced by malignant thyrocytes. As a result, its blood level is indistinguishable from that of a healthy person. <ref>PMID: 762873</ref><ref>DOI 21649472</ref>	+	For example, [https://en.wikipedia.org/wiki/Thyroidectomy thyroidectomy] and a iodine-131 therapy can be performed to cure thyroid cancer with an 80% chance. Following removal and iodine-131 therapy, thyroglobulin is this time produced by malignant thyrocytes. As a result, its blood level is indistinguishable from that of a healthy person. <ref>PMID: 762873</ref><ref>DOI 21649472</ref>
	But in case of recurrence and persistence of cancer, its level can increase again. Thyroglobulin therefore always serves as a tumor marker allowing us to estimate the risk of recurrence (>2ng/ml) or persistence (>1ng/ml) or remission.<ref>DOI 10.1677/ERC-10-0292</ref>		But in case of recurrence and persistence of cancer, its level can increase again. Thyroglobulin therefore always serves as a tumor marker allowing us to estimate the risk of recurrence (>2ng/ml) or persistence (>1ng/ml) or remission.<ref>DOI 10.1677/ERC-10-0292</ref>

Antoine Lambert: replace ntd

Antoine Lambert — Mon, 17 Jan 2022 15:52:42 GMT

replace ntd

←Older revision		Revision as of 15:52, 17 January 2022
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	Each of its monomers comprises '''5 distinct regions''' on which approximately 66 <scene name='86/868183/Tyr/1'>tyrosines</scene> (chain A in blue, chain B in green, chain C in dark red, chain D in light red) are distributed. These are the regions :		Each of its monomers comprises '''5 distinct regions''' on which approximately 66 <scene name='86/868183/Tyr/1'>tyrosines</scene> (chain A in blue, chain B in green, chain C in dark red, chain D in light red) are distributed. These are the regions :
-	<scene name='86/868183/Ntd/5'>N-terminal domain (NTD)</scene> [[https://www.youtube.com/watch?v=MuFHlCZCetU&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=5>NTD]], <scene name='86/868183/Core/4'>Core</scene> [[https://www.youtube.com/watch?v=Lx1G1KGxKN8&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=8>CORE]], <scene name='86/868183/Flap/4'>Flap</scene> [[https://www.youtube.com/watch?v=vk60Rdyo28A&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=6>FLAP]], <scene name='86/868183/Arm/3'>Arm</scene> [[https://www.youtube.com/watch?v=XzeTjQKfO0E&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=9>ARM]] and <scene name='86/868183/Ctd/4'>C-Terminal Domain (CTD)</scene> [[https://www.youtube.com/watch?v=N-mg_xj-deI&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=7>CTD]].	+	<scene name='86/868183/Ntd/6'>N-terminal domain (NTD)</scene> [[https://www.youtube.com/watch?v=MuFHlCZCetU&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=5>NTD]], <scene name='86/868183/Core/4'>Core</scene> [[https://www.youtube.com/watch?v=Lx1G1KGxKN8&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=8>CORE]], <scene name='86/868183/Flap/4'>Flap</scene> [[https://www.youtube.com/watch?v=vk60Rdyo28A&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=6>FLAP]], <scene name='86/868183/Arm/3'>Arm</scene> [[https://www.youtube.com/watch?v=XzeTjQKfO0E&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=9>ARM]] and <scene name='86/868183/Ctd/4'>C-Terminal Domain (CTD)</scene> [[https://www.youtube.com/watch?v=N-mg_xj-deI&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=7>CTD]].

	The <scene name='86/868183/Ctd/4'>carboxyl-terminal domain</scene> of TG (about 520 amino acids) shows homology with the [[Acetylcholinesterase]] and other esterases.		The <scene name='86/868183/Ctd/4'>carboxyl-terminal domain</scene> of TG (about 520 amino acids) shows homology with the [[Acetylcholinesterase]] and other esterases.

Antoine Lambert: disulf bond & ctd

Antoine Lambert — Mon, 17 Jan 2022 15:42:19 GMT

disulf bond & ctd

←Older revision		Revision as of 15:42, 17 January 2022
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	<scene name='86/868183/Ntd/5'>N-terminal domain (NTD)</scene> [[https://www.youtube.com/watch?v=MuFHlCZCetU&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=5>NTD]], <scene name='86/868183/Core/4'>Core</scene> [[https://www.youtube.com/watch?v=Lx1G1KGxKN8&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=8>CORE]], <scene name='86/868183/Flap/4'>Flap</scene> [[https://www.youtube.com/watch?v=vk60Rdyo28A&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=6>FLAP]], <scene name='86/868183/Arm/3'>Arm</scene> [[https://www.youtube.com/watch?v=XzeTjQKfO0E&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=9>ARM]] and <scene name='86/868183/Ctd/4'>C-Terminal Domain (CTD)</scene> [[https://www.youtube.com/watch?v=N-mg_xj-deI&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=7>CTD]].		<scene name='86/868183/Ntd/5'>N-terminal domain (NTD)</scene> [[https://www.youtube.com/watch?v=MuFHlCZCetU&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=5>NTD]], <scene name='86/868183/Core/4'>Core</scene> [[https://www.youtube.com/watch?v=Lx1G1KGxKN8&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=8>CORE]], <scene name='86/868183/Flap/4'>Flap</scene> [[https://www.youtube.com/watch?v=vk60Rdyo28A&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=6>FLAP]], <scene name='86/868183/Arm/3'>Arm</scene> [[https://www.youtube.com/watch?v=XzeTjQKfO0E&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=9>ARM]] and <scene name='86/868183/Ctd/4'>C-Terminal Domain (CTD)</scene> [[https://www.youtube.com/watch?v=N-mg_xj-deI&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=7>CTD]].

-	The carboxyl-terminal domain of TG (about 520 amino acids) shows homology with the [[Acetylcholinesterase]] and other esterases.	+	The <scene name='86/868183/Ctd/4'>carboxyl-terminal domain</scene> of TG (about 520 amino acids) shows homology with the [[Acetylcholinesterase]] and other esterases.

-	In addition, <scene name='86/868183/Tg/2'>TG</scene> has about 120 cysteine residues allowing the formation of about 60 disulfide bridge bonds per <scene name='86/868183/Monomer_tg/1'>monomer</scene> [[https://www.youtube.com/watch?v=Nuryu1aSqvY&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=11>Disulfide bridge]]. It confers great stability and solubility.	+	In addition, <scene name='86/868183/Tg/2'>TG</scene> has about 120 cysteine residues allowing the formation of about 60 <scene name='86/868183/Ssbonds/1'>disulfide bridge bonds</scene> per <scene name='86/868183/Monomer_tg/1'>monomer</scene> [[https://www.youtube.com/watch?v=Nuryu1aSqvY&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=11>Disulfide bridge]]. It confers great stability and solubility.

	These enzymes belong to the class of α-β hydrolase fold superfamily, characterized by α–helices and β-strands that roughly alternate along the polypeptide chain.<ref name="jeso">DOI 26595189</ref>		These enzymes belong to the class of α-β hydrolase fold superfamily, characterized by α–helices and β-strands that roughly alternate along the polypeptide chain.<ref name="jeso">DOI 26595189</ref>

Antoine Lambert at 12:27, 17 January 2022

Antoine Lambert — Mon, 17 Jan 2022 12:27:54 GMT

←Older revision		Revision as of 12:27, 17 January 2022
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	'''Introduction'''		'''Introduction'''
-	[https://en.wikipedia.org/wiki/Thyroglobulin Human thyroglobulin (TG)] is a precursor of two [https://en.wikipedia.org/wiki/Thyroid_hormones thyroid hormones] (TH): tetraiodothyronine or [[thyroxine]] (T4) and [[triiodothyronine (T3)]], ~~two thyroid hormones (TH)~~ essential for '''growth''', '''development''' and the '''control of metabolism'''. Its structure is essential for the diagnosis, treatment and monitoring of thyroid-related diseases.	+	[https://en.wikipedia.org/wiki/Thyroglobulin Human thyroglobulin (TG)] is a precursor of two [https://en.wikipedia.org/wiki/Thyroid_hormones thyroid hormones] (TH): tetraiodothyronine or [[thyroxine]] (T4) and [[triiodothyronine (T3)]], essential for '''growth''', '''development''' and the '''control of metabolism'''. Its structure is essential for the diagnosis, treatment and monitoring of thyroid-related diseases.


	== Composition and 3D structure <ref>DOI 32025030</ref> ==		== Composition and 3D structure <ref>DOI 32025030</ref> ==
	=== Global structure ===		=== Global structure ===
-	'''Human thyroglobulin''' is a dimeric glycoprotein (see a <scene name='86/868183/Monomer_tg/1'>monomer</scene>)consisting of 2 times '''2749 amino acid residues''' with a molecular weight of '''660 kDa'''. The average size of the dimer is '''120x235 Å'''.	+	'''Human thyroglobulin''' is a dimeric glycoprotein (see a <scene name='86/868183/Monomer_tg/1'>monomer</scene>) consisting of 2 times '''2749 amino acid residues''' with a molecular weight of '''660 kDa'''. The average size of the dimer is '''120x235 Å'''.

	Each of its monomers comprises '''5 distinct regions''' on which approximately 66 <scene name='86/868183/Tyr/1'>tyrosines</scene> (chain A in blue, chain B in green, chain C in dark red, chain D in light red) are distributed. These are the regions :		Each of its monomers comprises '''5 distinct regions''' on which approximately 66 <scene name='86/868183/Tyr/1'>tyrosines</scene> (chain A in blue, chain B in green, chain C in dark red, chain D in light red) are distributed. These are the regions :

Antoine Lambert at 12:26, 17 January 2022

Antoine Lambert — Mon, 17 Jan 2022 12:26:38 GMT

←Older revision		Revision as of 12:26, 17 January 2022
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	<scene name='86/868183/Ntd/5'>N-terminal domain (NTD)</scene> [[https://www.youtube.com/watch?v=MuFHlCZCetU&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=5>NTD]], <scene name='86/868183/Core/4'>Core</scene> [[https://www.youtube.com/watch?v=Lx1G1KGxKN8&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=8>CORE]], <scene name='86/868183/Flap/4'>Flap</scene> [[https://www.youtube.com/watch?v=vk60Rdyo28A&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=6>FLAP]], <scene name='86/868183/Arm/3'>Arm</scene> [[https://www.youtube.com/watch?v=XzeTjQKfO0E&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=9>ARM]] and <scene name='86/868183/Ctd/4'>C-Terminal Domain (CTD)</scene> [[https://www.youtube.com/watch?v=N-mg_xj-deI&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=7>CTD]].		<scene name='86/868183/Ntd/5'>N-terminal domain (NTD)</scene> [[https://www.youtube.com/watch?v=MuFHlCZCetU&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=5>NTD]], <scene name='86/868183/Core/4'>Core</scene> [[https://www.youtube.com/watch?v=Lx1G1KGxKN8&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=8>CORE]], <scene name='86/868183/Flap/4'>Flap</scene> [[https://www.youtube.com/watch?v=vk60Rdyo28A&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=6>FLAP]], <scene name='86/868183/Arm/3'>Arm</scene> [[https://www.youtube.com/watch?v=XzeTjQKfO0E&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=9>ARM]] and <scene name='86/868183/Ctd/4'>C-Terminal Domain (CTD)</scene> [[https://www.youtube.com/watch?v=N-mg_xj-deI&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=7>CTD]].

-	The carboxyl-terminal domain of TG (about 520 amino acids) shows homology with the [~~https://en.wikipedia.org/wiki/Acetylcholinesterase/~~ Acetylcholinesterase] and other esterases.	+	The carboxyl-terminal domain of TG (about 520 amino acids) shows homology with the [[Acetylcholinesterase]] and other esterases.

	In addition, <scene name='86/868183/Tg/2'>TG</scene> has about 120 cysteine residues allowing the formation of about 60 disulfide bridge bonds per <scene name='86/868183/Monomer_tg/1'>monomer</scene> [[https://www.youtube.com/watch?v=Nuryu1aSqvY&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=11>Disulfide bridge]]. It confers great stability and solubility.		In addition, <scene name='86/868183/Tg/2'>TG</scene> has about 120 cysteine residues allowing the formation of about 60 disulfide bridge bonds per <scene name='86/868183/Monomer_tg/1'>monomer</scene> [[https://www.youtube.com/watch?v=Nuryu1aSqvY&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=11>Disulfide bridge]]. It confers great stability and solubility.

Antoine Lambert: modif txt

Antoine Lambert — Mon, 17 Jan 2022 12:15:03 GMT

modif txt

←Older revision		Revision as of 12:15, 17 January 2022
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	'''Introduction'''		'''Introduction'''
-	[https://en.wikipedia.org/wiki/Thyroglobulin Human thyroglobulin (TG)] is a precursor of two [https://en.wikipedia.org/wiki/Thyroid_hormones thyroid hormones] (TH): tetraiodothyronine or [[thyroxine]] (T4) and [[triiodothyronine (T3)]], two thyroid hormones (TH). Its structure is essential for the diagnosis, treatment and monitoring of thyroid-related diseases.	+	[https://en.wikipedia.org/wiki/Thyroglobulin Human thyroglobulin (TG)] is a precursor of two [https://en.wikipedia.org/wiki/Thyroid_hormones thyroid hormones] (TH): tetraiodothyronine or [[thyroxine]] (T4) and [[triiodothyronine (T3)]], two thyroid hormones (TH) essential for '''growth''', '''development''' and the '''control of metabolism'''. Its structure is essential for the diagnosis, treatment and monitoring of thyroid-related diseases.


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	Each of its monomers comprises '''5 distinct regions''' on which approximately 66 <scene name='86/868183/Tyr/1'>tyrosines</scene> (chain A in blue, chain B in green, chain C in dark red, chain D in light red) are distributed. These are the regions :		Each of its monomers comprises '''5 distinct regions''' on which approximately 66 <scene name='86/868183/Tyr/1'>tyrosines</scene> (chain A in blue, chain B in green, chain C in dark red, chain D in light red) are distributed. These are the regions :
	<scene name='86/868183/Ntd/5'>N-terminal domain (NTD)</scene> [[https://www.youtube.com/watch?v=MuFHlCZCetU&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=5>NTD]], <scene name='86/868183/Core/4'>Core</scene> [[https://www.youtube.com/watch?v=Lx1G1KGxKN8&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=8>CORE]], <scene name='86/868183/Flap/4'>Flap</scene> [[https://www.youtube.com/watch?v=vk60Rdyo28A&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=6>FLAP]], <scene name='86/868183/Arm/3'>Arm</scene> [[https://www.youtube.com/watch?v=XzeTjQKfO0E&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=9>ARM]] and <scene name='86/868183/Ctd/4'>C-Terminal Domain (CTD)</scene> [[https://www.youtube.com/watch?v=N-mg_xj-deI&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=7>CTD]].		<scene name='86/868183/Ntd/5'>N-terminal domain (NTD)</scene> [[https://www.youtube.com/watch?v=MuFHlCZCetU&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=5>NTD]], <scene name='86/868183/Core/4'>Core</scene> [[https://www.youtube.com/watch?v=Lx1G1KGxKN8&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=8>CORE]], <scene name='86/868183/Flap/4'>Flap</scene> [[https://www.youtube.com/watch?v=vk60Rdyo28A&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=6>FLAP]], <scene name='86/868183/Arm/3'>Arm</scene> [[https://www.youtube.com/watch?v=XzeTjQKfO0E&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=9>ARM]] and <scene name='86/868183/Ctd/4'>C-Terminal Domain (CTD)</scene> [[https://www.youtube.com/watch?v=N-mg_xj-deI&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=7>CTD]].
-		+
-	In addition, <scene name='86/868183/Tg/2'>TG</scene> has about 120 cysteine residues allowing the formation of about 60 disulfide bridge bonds per <scene name='86/868183/Monomer_tg/1'>monomer</scene> [[https://www.youtube.com/watch?v=Nuryu1aSqvY&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=11>Disulfide bridge]]. It ~~is therefore a very stable~~ and ~~soluble protein~~.	+	The carboxyl-terminal domain of TG (about 520 amino acids) shows homology with the [https://en.wikipedia.org/wiki/Acetylcholinesterase/ Acetylcholinesterase] and other esterases.
		+
		+	In addition, <scene name='86/868183/Tg/2'>TG</scene> has about 120 cysteine residues allowing the formation of about 60 disulfide bridge bonds per <scene name='86/868183/Monomer_tg/1'>monomer</scene> [[https://www.youtube.com/watch?v=Nuryu1aSqvY&list=PLMGnv0h7EIJydYifu7JSxrkXMzpwlkyDF&index=11>Disulfide bridge]]. It confers great stability and solubility.
		+
		+	These enzymes belong to the class of α-β hydrolase fold superfamily, characterized by α–helices and β-strands that roughly alternate along the polypeptide chain.<ref name="jeso">DOI 26595189</ref>

	=== Structure of hormonogenic sites ===		=== Structure of hormonogenic sites ===
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	=== Post-translational modifications ===		=== Post-translational modifications ===
-	TG also undergoes N-glycosylations in the ER at <scene name='86/868183/Glycosylation_sites/1'>17 glycosylation sites</scene>, so that 10% of its molecular weight is carbohydrate. These modifications enhance its stability and solubility. Indeed, the two monomers are linked not by covalent interactions but via numerous interactions allowed by these N-glycosylations.	+	TG also undergoes N-glycosylations in the [https://en.wikipedia.org/wiki/Endoplasmic_reticulum/ endoplasmic reticulum] at <scene name='86/868183/Glycosylation_sites/1'>17 glycosylation sites</scene>, so that 10% of its molecular weight is carbohydrate. TG also undergoes maturation steps in this organelle, where it acquires dilsufide-bonds. These modifications enhance its stability and solubility. Indeed, the two monomers are linked not by covalent interactions but via numerous interactions allowed by these N-glycosylations.

	=== Folding ===		=== Folding ===
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	Once their 3D structure is acquired, TGs are exported into the colloid by exocytosis thanks to their signal peptide which will be cleaved. This extracellular storage increases the amount of TG stored in the body.		Once their 3D structure is acquired, TGs are exported into the colloid by exocytosis thanks to their signal peptide which will be cleaved. This extracellular storage increases the amount of TG stored in the body.

-	In the colloid, about '''30 tyrosines''' out of the '''66 tyrosines''', each consisting of a phenol group, are iodized. The quantity of iodinated tyrosine depends however on the iodide concentration of the colloid. Indeed, one or two iodide ions can be covalently bound to the colloid and thus give a '''di- (DIT)''' or '''mono-iodinated (MIT) phenol group'''. The iodination of the phenol groups is carried out by two membrane enzymes of the follicular cells: the double oxidase ('''DUOX''') synthesizes the hydrogen peroxide H2O2 necessary for thyroid peroxidase ('''TPO''').	+	In the colloid, about '''30 tyrosines''' out of the '''66 tyrosines''', each consisting of a phenol group, are iodized. The quantity of iodinated tyrosine depends however on the iodide concentration of the colloid. Indeed, one or two iodide ions can be covalently bound to the colloid and thus give a '''di- (DIT)''' or '''mono-iodinated (MIT) phenol group'''. The iodination of the phenol groups is carried out by two membrane enzymes of the follicular cells: the double oxidase ('''DUOX''') synthesizes the hydrogen peroxide H2O2 necessary for thyroid peroxidase ('''TPO'''). The synthesis is completed by TG proteolysis.

	Due to the spatial conformation of <scene name='86/868183/Tg/3'>TG</scene>, there is a transfer of di- or mono-iodinated aromatic ring from a donor tyrosine to a close acceptor diiodotyrosine for the 14 tyrosines of the hormonogenic sites. Acceptor iodinated tyrosines are DITs because they are deprotonated due to their 6.5 acid pka facilitating the acceptance reaction leading to the formation of quinol-ether bonds, whereas donor iodinated tyrosines are MITs with a pKa of 8.5<ref>DOI 10.1530/eje.0.1380227</ref>.		Due to the spatial conformation of <scene name='86/868183/Tg/3'>TG</scene>, there is a transfer of di- or mono-iodinated aromatic ring from a donor tyrosine to a close acceptor diiodotyrosine for the 14 tyrosines of the hormonogenic sites. Acceptor iodinated tyrosines are DITs because they are deprotonated due to their 6.5 acid pka facilitating the acceptance reaction leading to the formation of quinol-ether bonds, whereas donor iodinated tyrosines are MITs with a pKa of 8.5<ref>DOI 10.1530/eje.0.1380227</ref>.
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	The complex and particularly stable structure of <scene name='86/868183/Tg/3'>TG</scene> gives it iodide reservoir properties. Indeed, all iodinated but non-hormonoid tyrosines are useful for iodine storage in the thyroid gland.		The complex and particularly stable structure of <scene name='86/868183/Tg/3'>TG</scene> gives it iodide reservoir properties. Indeed, all iodinated but non-hormonoid tyrosines are useful for iodine storage in the thyroid gland.

-	== Interest in the medical field<ref>DOI 6814409</ref><ref>DOI 29984794</ref><ref~~>DOI 26595189<~~/~~ref~~> ==	+	== Interest in the medical field<ref>DOI 6814409</ref><ref>DOI 29984794</ref><ref name="jeso"/> ==
	=== Modification of the TG quantity related to the desease ===		=== Modification of the TG quantity related to the desease ===
	A healthy subject has between '''5 and 25 µg of TG per liter''' of blood.<ref>DOI 5773064</ref> In case of thyroid dysfunction, this level may increase or decrease. For example, it decreases in the case of congenital athyreosis (insufficiency of the thyroid gland) or prior to a miscarriage due to the presence of anti-TG antibodies, but increases in the case of cancer, thyroiditis, inflammation of the thyroid or autoimmune thyroid diseases '''AITD''' <ref>DOI 24147207</ref>(Grave's disease, Hashimoto's thyroiditis).<ref>DOI 11788684</ref><ref>DOI 17614775</ref>		A healthy subject has between '''5 and 25 µg of TG per liter''' of blood.<ref>DOI 5773064</ref> In case of thyroid dysfunction, this level may increase or decrease. For example, it decreases in the case of congenital athyreosis (insufficiency of the thyroid gland) or prior to a miscarriage due to the presence of anti-TG antibodies, but increases in the case of cancer, thyroiditis, inflammation of the thyroid or autoimmune thyroid diseases '''AITD''' <ref>DOI 24147207</ref>(Grave's disease, Hashimoto's thyroiditis).<ref>DOI 11788684</ref><ref>DOI 17614775</ref>