User:Marianne Weulersse/Sandbox 202 - Revision history

Marianne Weulersse at 12:37, 30 July 2013

Marianne Weulersse — Tue, 30 Jul 2013 12:37:23 GMT

←Older revision		Revision as of 12:37, 30 July 2013
Line 1:		Line 1:
-	Pauline TRISTRAM and Marianne WEULERSSE'''THE HUMAN SRY-DNA COMPLEX'''	+	Pauline TRISTRAM and Marianne WEULERSSE: '''THE HUMAN SRY-DNA COMPLEX'''
	----		----

Marianne Weulersse at 12:37, 30 July 2013

Marianne Weulersse — Tue, 30 Jul 2013 12:37:08 GMT

←Older revision		Revision as of 12:37, 30 July 2013
Line 1:		Line 1:
-	'''THE HUMAN SRY-DNA COMPLEX'''	+	Pauline TRISTRAM and Marianne WEULERSSE'''THE HUMAN SRY-DNA COMPLEX'''
	----		----

Marianne Weulersse at 20:22, 2 January 2012

Marianne Weulersse — Mon, 02 Jan 2012 20:22:02 GMT

←Older revision		Revision as of 20:22, 2 January 2012
Line 1:		Line 1:
		+	'''THE HUMAN SRY-DNA COMPLEX'''
		+	----
		+
		+
	== Introduction ==		== Introduction ==

Marianne Weulersse at 19:36, 2 January 2012

Marianne Weulersse — Mon, 02 Jan 2012 19:36:13 GMT

←Older revision		Revision as of 19:36, 2 January 2012
Line 2:		Line 2:


-	The human protein SRY (hSRY) is a '''transcription factor''' implicated in the differentiation of ~~the~~ gonads during development.	+	The human protein SRY (hSRY) is a '''transcription factor''' implicated in the differentiation of gonads during development.
	SRY is encoded by the SRY gene located on the human chromosome Y and consists of 223 residues which comprises three domains: N-terminal domain, central DNA-binding domain called High Mobility Group (HMG) box and the C-terminal domain.		SRY is encoded by the SRY gene located on the human chromosome Y and consists of 223 residues which comprises three domains: N-terminal domain, central DNA-binding domain called High Mobility Group (HMG) box and the C-terminal domain.

Line 60:		Line 60:
	The major structural change occurs in the long arm of the L-shaped conformation of the hSRY-HMG domain. The angle between the long and short arms is more obtuse to accommodate the DNA through the sway of the extended N- and C-termini.		The major structural change occurs in the long arm of the L-shaped conformation of the hSRY-HMG domain. The angle between the long and short arms is more obtuse to accommodate the DNA through the sway of the extended N- and C-termini.
	The aromatic sidechains of Phe12, packed against DNA bases, lay at the horizontal level with <scene name='User:Marianne_Weulersse/Sandbox_202/Ile13/4'>Ile13</scene> which deform the DNA. '''Met9''' and''' Trp43''' bind the sugar phosphate backbone thereby opening the minor groove.		The aromatic sidechains of Phe12, packed against DNA bases, lay at the horizontal level with <scene name='User:Marianne_Weulersse/Sandbox_202/Ile13/4'>Ile13</scene> which deform the DNA. '''Met9''' and''' Trp43''' bind the sugar phosphate backbone thereby opening the minor groove.
-	<scene name='User:Marianne_Weulersse/Sandbox_202/Met9/2'>Met9</scene> is an important aliphatic residue of the big hydrophobic core located at the joint of the extended N-terminal and the helix 1, close to the intercalating residue Ile13 and in contact with the backbone of DNA. ''Ile13 could be affected by the sway of Met9'' and becomes more feasible to intercalate into the basepairs of DNA. Met9 mutations would result in a decrease of the binding affinity and/or bending angles. The naturally occuring mutation Met9 => Ile would reduce the swing because of the shorter sidechain of Ile( -CH3 branch in the {{Template:ColorKey_Element_C}}α atom). The swing of Ile is therefore too weak to help the intercalation of Ile13. As a result, the angle of ~~DNAbending~~ decreases and the affinity of ~~DNAbinding~~ reduces.	+	<scene name='User:Marianne_Weulersse/Sandbox_202/Met9/2'>Met9</scene> is an important aliphatic residue of the big hydrophobic core located at the joint of the extended N-terminal and the helix 1, close to the intercalating residue Ile13 and in contact with the backbone of DNA. ''Ile13 could be affected by the sway of Met9'' and becomes more feasible to intercalate into the basepairs of DNA. Met9 mutations would result in a decrease of the binding affinity and/or bending angles. The naturally occuring mutation Met9 => Ile would reduce the swing because of the shorter sidechain of Ile( -CH3 branch in the {{Template:ColorKey_Element_C}}α atom). The swing of Ile is therefore too weak to help the intercalation of Ile13. As a result, the angle of DNA bending decreases and the affinity of DNA binding reduces.
	The conformation change (deviations) of the short loop region around Met9 is essential to the function of SRY.		The conformation change (deviations) of the short loop region around Met9 is essential to the function of SRY.

Marianne Weulersse at 17:15, 2 January 2012

Marianne Weulersse — Mon, 02 Jan 2012 17:15:17 GMT

←Older revision		Revision as of 17:15, 2 January 2012
Line 32:		Line 32:

	The <scene name='User:Marianne_Weulersse/Sandbox_202/Hmg_box/4'>HMG box</scene> binds specifically DNA sequence through the minor groove (more hydrophobic than the major groove, especially the adenine base which has no -NH2 group).		The <scene name='User:Marianne_Weulersse/Sandbox_202/Hmg_box/4'>HMG box</scene> binds specifically DNA sequence through the minor groove (more hydrophobic than the major groove, especially the adenine base which has no -NH2 group).
-	Its '''sequence specificity''' is related with <scene name='User:Marianne_Weulersse/Sandbox_202/Pro70/1'>Pro70</scene> included in the conserved basic terminal tail of the HMG box, which trigger the C-terminal region to bend toward the N-terminus and with <scene name='User:Marianne_Weulersse/Sandbox_202/Hydrophobic_residues/3'>hydrophobic residues</scene> packed together.	+	Its '''sequence specificity''' is related with <scene name='User:Marianne_Weulersse/Sandbox_202/Pro70/1'>Pro70</scene> included in the conserved basic terminal tail of the HMG box <ref>PMID:16504207</ref>, which trigger the C-terminal region to bend toward the N-terminus and with <scene name='User:Marianne_Weulersse/Sandbox_202/Hydrophobic_residues/3'>hydrophobic residues</scene> packed together.

	== Protein binding and conformation changes ==		== Protein binding and conformation changes ==

Marianne Weulersse at 17:08, 2 January 2012

Marianne Weulersse — Mon, 02 Jan 2012 17:08:20 GMT

←Older revision		Revision as of 17:08, 2 January 2012
Line 32:		Line 32:

	The <scene name='User:Marianne_Weulersse/Sandbox_202/Hmg_box/4'>HMG box</scene> binds specifically DNA sequence through the minor groove (more hydrophobic than the major groove, especially the adenine base which has no -NH2 group).		The <scene name='User:Marianne_Weulersse/Sandbox_202/Hmg_box/4'>HMG box</scene> binds specifically DNA sequence through the minor groove (more hydrophobic than the major groove, especially the adenine base which has no -NH2 group).
-	Its '''sequence specificity''' is related with <scene name='User:Marianne_Weulersse/Sandbox_202/Pro70/1'>Pro70</scene>,included in the basic terminal tail of the HMG box, which trigger the C-terminal region to bend toward the N-terminus and with <scene name='User:Marianne_Weulersse/Sandbox_202/Hydrophobic_residues/3'>hydrophobic residues</scene> packed together.	+	Its '''sequence specificity''' is related with <scene name='User:Marianne_Weulersse/Sandbox_202/Pro70/1'>Pro70</scene> included in the conserved basic terminal tail of the HMG box, which trigger the C-terminal region to bend toward the N-terminus and with <scene name='User:Marianne_Weulersse/Sandbox_202/Hydrophobic_residues/3'>hydrophobic residues</scene> packed together.

	== Protein binding and conformation changes ==		== Protein binding and conformation changes ==

Marianne Weulersse at 17:06, 2 January 2012

Marianne Weulersse — Mon, 02 Jan 2012 17:06:51 GMT

←Older revision		Revision as of 17:06, 2 January 2012
Line 32:		Line 32:

	The <scene name='User:Marianne_Weulersse/Sandbox_202/Hmg_box/4'>HMG box</scene> binds specifically DNA sequence through the minor groove (more hydrophobic than the major groove, especially the adenine base which has no -NH2 group).		The <scene name='User:Marianne_Weulersse/Sandbox_202/Hmg_box/4'>HMG box</scene> binds specifically DNA sequence through the minor groove (more hydrophobic than the major groove, especially the adenine base which has no -NH2 group).
-	Its '''sequence specificity''' is related with <scene name='User:Marianne_Weulersse/Sandbox_202/Pro70/1'>Pro70</scene> which trigger the C-terminal region to bend toward the N-terminus and with <scene name='User:Marianne_Weulersse/Sandbox_202/Hydrophobic_residues/3'>hydrophobic residues</scene> packed together.	+	Its '''sequence specificity''' is related with <scene name='User:Marianne_Weulersse/Sandbox_202/Pro70/1'>Pro70</scene>,included in the basic terminal tail of the HMG box, which trigger the C-terminal region to bend toward the N-terminus and with <scene name='User:Marianne_Weulersse/Sandbox_202/Hydrophobic_residues/3'>hydrophobic residues</scene> packed together.
-		+

	== Protein binding and conformation changes ==		== Protein binding and conformation changes ==

Marianne Weulersse at 16:43, 2 January 2012

Marianne Weulersse — Mon, 02 Jan 2012 16:43:00 GMT

←Older revision		Revision as of 16:43, 2 January 2012
Line 85:		Line 85:


-	Many sequencing showed that the SRY protein differs from one species to another except for the HMG domain that remains preserved.The main influence of the SRY gene regulation comes from the structural alteration of the promoter of the target DNA.	+	Many sequencing showed that the SRY protein differs from one species to another except for the HMG domain that remains preserved.The main influence of the SRY gene regulation comes from the ''structural alteration of the promoter'' of the target DNA.


Line 91:		Line 91:
	== Conclusion ==		== Conclusion ==

-	SRY acts as a transcriptional activator by binding specifically to the sequence DNA octamer target site AACAA-(A/T)(G/C) of the MIS gene promoter (Müllerian Inhibiting Substance). Therefore, the conformational change of the DNA latter allows it to be recognized by other transcription factors inducing the transcription of genes implicated in the development of the male reproductive system. The MIS gene codes for a substance to cause regression of the female genital tract such as the precursor of the uterus, upper vagina and fallopian tube. SRY may act also as a transcriptional repressor by binding the cytochrome P450 aromatase promoter, enabling the conversion of testosterone to estradiol in order to promote the development of the testes.	+	SRY acts as a transcriptional activator by binding specifically to the sequence DNA octamer target site AACAA-(A/T)(G/C) of the''' MIS gene''' promoter (Müllerian Inhibiting Substance). Therefore, the conformational change of the DNA latter allows it to be recognized by other transcription factors inducing the transcription of genes implicated in the development of the male reproductive system. The MIS gene codes for a substance which cause regression of the female genital tract such as the precursor of the uterus, upper vagina and fallopian tube. SRY may act also as a '''transcriptional repressor''' by binding the ''cytochrome P450 aromatase promoter'', enabling the conversion of testosterone to estradiol in order to promote the development of the testes.

	== References ==		== References ==

	<references/>		<references/>

Marianne Weulersse at 16:39, 2 January 2012

Marianne Weulersse — Mon, 02 Jan 2012 16:39:36 GMT

←Older revision		Revision as of 16:39, 2 January 2012
Line 80:		Line 80:
	The hydroxyl groups of residues are used to develop '''water-mediated hydrogen bonds''' with the nitrogen atoms of DNA bases (Ser33 forms a hydrogen bond with the N2 atom of G9).They participate to the specific SRY-HMG-DNA interaction and allow the strong bond of the protein.		The hydroxyl groups of residues are used to develop '''water-mediated hydrogen bonds''' with the nitrogen atoms of DNA bases (Ser33 forms a hydrogen bond with the N2 atom of G9).They participate to the specific SRY-HMG-DNA interaction and allow the strong bond of the protein.
	*There are five ''direct'' hydrogen bonds (one between the hydroxyl group of Ser36 and the O2 atom of T10 and the others between the protein and DNA phosphate backbone).		*There are five ''direct'' hydrogen bonds (one between the hydroxyl group of Ser36 and the O2 atom of T10 and the others between the protein and DNA phosphate backbone).
-	*One <scene name='User:Marianne_Weulersse/Sandbox_202/~~Hydrogens_bons~~/1'>water bridge</scene> is located between Asn10 and the O2 atom of C4 and T14.	+	*One <scene name='User:Marianne_Weulersse/Sandbox_202/Wtaer_bridge/1'>water bridge</scene> is located between Asn10 and the O2 atom of C4 and T14.

	== Sequence conservation ==		== Sequence conservation ==

Marianne Weulersse at 16:28, 2 January 2012

Marianne Weulersse — Mon, 02 Jan 2012 16:28:56 GMT

←Older revision		Revision as of 16:28, 2 January 2012
Line 52:		Line 52:


-	===== ~~Hydrophobic~~ Recognition =====	+	===== {{Template:ColorKey_Hydrophobic}} Recognition =====


Line 61:		Line 61:
	The major structural change occurs in the long arm of the L-shaped conformation of the hSRY-HMG domain. The angle between the long and short arms is more obtuse to accommodate the DNA through the sway of the extended N- and C-termini.		The major structural change occurs in the long arm of the L-shaped conformation of the hSRY-HMG domain. The angle between the long and short arms is more obtuse to accommodate the DNA through the sway of the extended N- and C-termini.
	The aromatic sidechains of Phe12, packed against DNA bases, lay at the horizontal level with <scene name='User:Marianne_Weulersse/Sandbox_202/Ile13/4'>Ile13</scene> which deform the DNA. '''Met9''' and''' Trp43''' bind the sugar phosphate backbone thereby opening the minor groove.		The aromatic sidechains of Phe12, packed against DNA bases, lay at the horizontal level with <scene name='User:Marianne_Weulersse/Sandbox_202/Ile13/4'>Ile13</scene> which deform the DNA. '''Met9''' and''' Trp43''' bind the sugar phosphate backbone thereby opening the minor groove.
-	<scene name='User:Marianne_Weulersse/Sandbox_202/Met9/2'>Met9</scene> is an important aliphatic residue of the big hydrophobic core located at the joint of the extended N-terminal and the helix 1, close to the intercalating residue Ile13 and in contact with the backbone of DNA. ''Ile13 could be affected by the sway of Met9'' and becomes more feasible to intercalate into the basepairs of DNA. Met9 mutations would result in a decrease of the binding affinity and/or bending angles. The naturally occuring mutation Met9 => Ile would reduce the swing because of the shorter sidechain of Ile( -CH3 branch in the Cα atom). The swing of Ile is therefore too weak to help the intercalation of Ile13. As a result, the angle of DNAbending decreases and the affinity of DNAbinding reduces.	+	<scene name='User:Marianne_Weulersse/Sandbox_202/Met9/2'>Met9</scene> is an important aliphatic residue of the big hydrophobic core located at the joint of the extended N-terminal and the helix 1, close to the intercalating residue Ile13 and in contact with the backbone of DNA. ''Ile13 could be affected by the sway of Met9'' and becomes more feasible to intercalate into the basepairs of DNA. Met9 mutations would result in a decrease of the binding affinity and/or bending angles. The naturally occuring mutation Met9 => Ile would reduce the swing because of the shorter sidechain of Ile( -CH3 branch in the {{Template:ColorKey_Element_C}}α atom). The swing of Ile is therefore too weak to help the intercalation of Ile13. As a result, the angle of DNAbending decreases and the affinity of DNAbinding reduces.
	The conformation change (deviations) of the short loop region around Met9 is essential to the function of SRY.		The conformation change (deviations) of the short loop region around Met9 is essential to the function of SRY.