Sandbox Reserved 1123 - Revision history

Loïc Duffet at 12:58, 29 January 2016

Loïc Duffet — Fri, 29 Jan 2016 12:58:34 GMT

←Older revision		Revision as of 12:58, 29 January 2016
Line 22:		Line 22:
	Each HIV-1 virus owns a '''conical core capsid''' that encapsulates the ssRNA(+) viral genome and some viral enzymes that are essential for the host infection. This capsid contains '''about 250 hexamers and 12 pentamers of the CA protein''', pentamers are important to generate the curvature of the structure. This capsid is the mature capsid, its formation results in the maturation and disassembly of the immature gag polyproteins (first structural protein products which are encoded by the HIV-1 genome) by viral proteases. CA proteins are organized in '''two domains''': an N-terminal domain ( <scene name='71/719864/Ntd_capsid/1'>NTD </scene>) and a C-terminal domain (<scene name='71/719864/Ctd/2'>CTD </scene>). The mature capsid is formed by the assembly of approximately two-thirds of the mature CA proteins in the viral particle. CA proteins bind together and organize themselves in order to create a '''lattice of hexameric rings''', these rings contain an '''inner ring of six <scene name='71/719864/Ntd_capsid/1'>NTD </scene>s''', surrounded by a '''belt of six <scene name='71/719864/Ctd/2'>CTD </scene>s'''. Then, 12 CA pentamers join the structure, it permits the formation of a closed protein shell. <ref name="C"/>		Each HIV-1 virus owns a '''conical core capsid''' that encapsulates the ssRNA(+) viral genome and some viral enzymes that are essential for the host infection. This capsid contains '''about 250 hexamers and 12 pentamers of the CA protein''', pentamers are important to generate the curvature of the structure. This capsid is the mature capsid, its formation results in the maturation and disassembly of the immature gag polyproteins (first structural protein products which are encoded by the HIV-1 genome) by viral proteases. CA proteins are organized in '''two domains''': an N-terminal domain ( <scene name='71/719864/Ntd_capsid/1'>NTD </scene>) and a C-terminal domain (<scene name='71/719864/Ctd/2'>CTD </scene>). The mature capsid is formed by the assembly of approximately two-thirds of the mature CA proteins in the viral particle. CA proteins bind together and organize themselves in order to create a '''lattice of hexameric rings''', these rings contain an '''inner ring of six <scene name='71/719864/Ntd_capsid/1'>NTD </scene>s''', surrounded by a '''belt of six <scene name='71/719864/Ctd/2'>CTD </scene>s'''. Then, 12 CA pentamers join the structure, it permits the formation of a closed protein shell. <ref name="C"/>

-	[[Image:capsid.jpg]]

	=== Primary structure ===		=== Primary structure ===

	CA proteins are composed of '''about 230 residues''' <ref> [http://www.rcsb.org/pdb/explore/explore.do?structureId=3H47 PDB File: 3H47] </ref> and as we mentioned above they contain two domains: <scene name='71/719864/Ntd_capsid/1'>NTD </scene> (in green) and <scene name='71/719864/Ctd/2'>CTD </scene> (in yellow). These two domains are linked together thanks to a <scene name='71/719864/Flexible_linker/2'>Flexible linker </scene> (in orange). <ref name="C"/>		CA proteins are composed of '''about 230 residues''' <ref> [http://www.rcsb.org/pdb/explore/explore.do?structureId=3H47 PDB File: 3H47] </ref> and as we mentioned above they contain two domains: <scene name='71/719864/Ntd_capsid/1'>NTD </scene> (in green) and <scene name='71/719864/Ctd/2'>CTD </scene> (in yellow). These two domains are linked together thanks to a <scene name='71/719864/Flexible_linker/2'>Flexible linker </scene> (in orange). <ref name="C"/>
		+
		+	[[Image:capsid.jpg]]

	=== Tertiary structure ===		=== Tertiary structure ===

Loïc Duffet at 12:56, 29 January 2016

Loïc Duffet — Fri, 29 Jan 2016 12:56:22 GMT

←Older revision		Revision as of 12:56, 29 January 2016
Line 73:		Line 73:

	This approach is interesting because, based on structural information, we are able to build such ligands using drug design. However, we are still far away from the "miraculous HIV drug", because the pathway from design to approved drug is not an easy way at all.		This approach is interesting because, based on structural information, we are able to build such ligands using drug design. However, we are still far away from the "miraculous HIV drug", because the pathway from design to approved drug is not an easy way at all.
		+
		+

Loïc Duffet at 12:55, 29 January 2016

Loïc Duffet — Fri, 29 Jan 2016 12:55:38 GMT

←Older revision		Revision as of 12:55, 29 January 2016
Line 73:		Line 73:

	This approach is interesting because, based on structural information, we are able to build such ligands using drug design. However, we are still far away from the "miraculous HIV drug", because the pathway from design to approved drug is not an easy way at all.		This approach is interesting because, based on structural information, we are able to build such ligands using drug design. However, we are still far away from the "miraculous HIV drug", because the pathway from design to approved drug is not an easy way at all.
		+
		+
		+
		+
		+
		+
		+

Loïc Duffet at 12:54, 29 January 2016

Loïc Duffet — Fri, 29 Jan 2016 12:54:55 GMT

←Older revision		Revision as of 12:54, 29 January 2016
Line 35:		Line 35:
	=== Quaternary structure ===		=== Quaternary structure ===

-	CA hexamers formation is due to intermolecular highly cooperative and noncovalent interactions, between the NTD of one subunit and the CTD of the neighbouring subunit within the same hexameric ring. These NTD-CTD interactions are crucial for the HIV-1 capsid assembly. CTD-CTD contacts and NTD-NTD contacts also exist for CA hexamers and pentamers formation. <ref name="C">[http://www.ncbi.nlm.nih.gov/pubmed/?term=%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BCStructural+basis+of+HIV-1+capsid+recognition+by+PF74+and+CPSF6 Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18625-30. doi: 10.1073/pnas.1419945112. Epub 2014 Dec 17.	+	CA hexamers formation is due to intermolecular highly cooperative and noncovalent interactions, between the NTD of one subunit and the CTD of the neighbouring subunit within the same hexameric ring. These '''NTD-CTD interactions are crucial for the HIV-1 capsid assembly'''. CTD-CTD contacts and NTD-NTD contacts also exist for CA hexamers and pentamers formation. <ref name="C">[http://www.ncbi.nlm.nih.gov/pubmed/?term=%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BCStructural+basis+of+HIV-1+capsid+recognition+by+PF74+and+CPSF6 Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18625-30. doi: 10.1073/pnas.1419945112. Epub 2014 Dec 17.
	Structural basis of HIV-1 capsid recognition by PF74 and CPSF6. Bhattacharya A, Alam SL, Fricke T, Zadrozny K, Sedzicki J, Taylor AB, Demeler B, Pornillos O, Ganser-Pornillos BK, Diaz-Griffero F, Ivanov DN, Yeager M.] </ref>		Structural basis of HIV-1 capsid recognition by PF74 and CPSF6. Bhattacharya A, Alam SL, Fricke T, Zadrozny K, Sedzicki J, Taylor AB, Demeler B, Pornillos O, Ganser-Pornillos BK, Diaz-Griffero F, Ivanov DN, Yeager M.] </ref>

-	NTD forms both hexameric or pentameric rings, while CTD forms symmetric homodimers which connect the rings into a hexagonal lattice. Moreover, the formation of hexamers and pentamers is controlled by an electrostatic switch, thanks to this process, hexamers are favored compared to pentamers. Pentamer and hexamer structures are very close to each other, in either case, the CTDs form a belt which encircles the inner ring of NTDs.	+	NTD forms both hexameric or pentameric rings, while CTD forms symmetric homodimers which connect the rings into a hexagonal lattice. Moreover, the formation of hexamers and pentamers is controlled by an electrostatic switch, thanks to this process, hexamers are favored compared to pentamers. '''Pentamer and hexamer structures are very close to each other''', in either case, the CTDs form a belt which encircles the inner ring of NTDs.
-	Intermolecular NTD-NTD contacts facilitate the formation of the NTD rings, while NTD-CTD contacts maintain the CTD subunits in the belts. There is no intramolecular interaction between the NTD and CTD of each subunit, except the peptidic linkage between these two domains of course. Furthermore, the flexible linker is able to adopt different conformations, which is very useful because the monomers can position themselves in an optimal manner to permit the interaction surfaces in pentamer and hexamer. NTD rings form a rigid structure, this is not the case of CTDs in belts which are mobile and able to rotate, relative to the NTD ring. CTD pivotes such as a rigid body about four intermolecular helix-capping hydrogen bounds at the NTD-CTD interface.	+
-	Thus, each hexameric ring can have slightly different dihedral angles relative to its adjacent rings thanks to the CTDs movments. NTD rings interactions are possible thanks to the first three α-helices of each subunit, they forme a 15-helix barrel in the pentamer and a 18-helix barrel in the hexamer. A small hydrophobic core is located at the center of the bundle thanks to the presence of aliphatic residues, while polar sidechains are present at the periphery and do hydrophilic interactions. <ref name="B"/> <ref>[http://www.ncbi.nlm.nih.gov/pubmed/?term=nature09640 Nature. 2011 Jan 20;469(7330):424-7. doi: 10.1038/nature09640. Atomic-level modelling of the HIV capsid. Pornillos O, Ganser-Pornillos BK, Yeager M.] </ref>	+	Intermolecular '''NTD-NTD contacts facilitate the formation of the NTD rings''', while '''NTD-CTD contacts maintain the CTD subunits in the belts'''. There is no intramolecular interaction between the NTD and CTD of each subunit, except the peptidic linkage between these two domains of course. Furthermore, the flexible linker is able to adopt different conformations, which is very useful because the monomers can position themselves in an optimal manner to permit the interaction surfaces in pentamer and hexamer. '''NTD rings form a rigid structure''', this is not the case of '''CTDs in belts''' which '''are mobile and able to rotate''', relative to the NTD ring. CTD pivotes such as a rigid body about four intermolecular helix-capping hydrogen bounds at the NTD-CTD interface.
		+
		+	Thus, each hexameric ring can have slightly different dihedral angles relative to its adjacent rings thanks to the CTDs movments. '''NTD rings interactions are possible thanks to the first three α-helices of each subunit''', they forme a 15-helix barrel in the pentamer and a 18-helix barrel in the hexamer. A small hydrophobic core is located at the center of the bundle thanks to the presence of aliphatic residues, while polar sidechains are present at the periphery and do hydrophilic interactions. <ref name="B"/> <ref>[http://www.ncbi.nlm.nih.gov/pubmed/?term=nature09640 Nature. 2011 Jan 20;469(7330):424-7. doi: 10.1038/nature09640. Atomic-level modelling of the HIV capsid. Pornillos O, Ganser-Pornillos BK, Yeager M.] </ref>


Line 71:		Line 73:

	This approach is interesting because, based on structural information, we are able to build such ligands using drug design. However, we are still far away from the "miraculous HIV drug", because the pathway from design to approved drug is not an easy way at all.		This approach is interesting because, based on structural information, we are able to build such ligands using drug design. However, we are still far away from the "miraculous HIV drug", because the pathway from design to approved drug is not an easy way at all.
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+

Loïc Duffet at 12:49, 29 January 2016

Loïc Duffet — Fri, 29 Jan 2016 12:49:29 GMT

←Older revision		Revision as of 12:49, 29 January 2016
Line 55:		Line 55:
	* Nuclear pore (certainly but not sure)<ref name="A">[http://www.google.fr/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0ahUKEwiV2fr01MzKAhWLhhoKHafGDaUQFggiMAA&url=http%3A%2F%2Fwww.nature.com%2Fnrmicro%2Fjournal%2Fv13%2Fn8%2Ffull%2Fnrmicro3503.html&usg=AFQjCNHxI2ZQfqG9K9oGRGsoomYd40gcgw HIV-1 capsid: the multifaceted key player in HIV-1 infection Nature Reviews Microbiology 13,471–483 (2015)doi:10.1038/nrmicro3503]</ref>		* Nuclear pore (certainly but not sure)<ref name="A">[http://www.google.fr/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0ahUKEwiV2fr01MzKAhWLhhoKHafGDaUQFggiMAA&url=http%3A%2F%2Fwww.nature.com%2Fnrmicro%2Fjournal%2Fv13%2Fn8%2Ffull%2Fnrmicro3503.html&usg=AFQjCNHxI2ZQfqG9K9oGRGsoomYd40gcgw HIV-1 capsid: the multifaceted key player in HIV-1 infection Nature Reviews Microbiology 13,471–483 (2015)doi:10.1038/nrmicro3503]</ref>
	* Dynein <ref name="A"/>		* Dynein <ref name="A"/>
		+	* CPSF6, TNPO3, NUP538/RanBP2 and nucleoporin 153 kDa (all these proteins are cellular transport factors)<ref name="C"/>
	* Integrase ?		* Integrase ?

Loïc Duffet at 12:45, 29 January 2016

Loïc Duffet — Fri, 29 Jan 2016 12:45:12 GMT

←Older revision		Revision as of 12:45, 29 January 2016
Line 26:		Line 26:
	=== Primary structure ===		=== Primary structure ===

-	CA proteins are composed of '''about 230 residues''' [4] and as we mentioned above they contain two domains: <scene name='71/719864/Ntd_capsid/1'>NTD </scene> (in green) and <scene name='71/719864/Ctd/2'>CTD </scene> (in yellow). These two domains are linked together thanks to a <scene name='71/719864/Flexible_linker/2'>Flexible linker </scene> (in orange). <ref name="C"/>	+	CA proteins are composed of '''about 230 residues''' <ref> [http://www.rcsb.org/pdb/explore/explore.do?structureId=3H47 PDB File: 3H47] </ref> and as we mentioned above they contain two domains: <scene name='71/719864/Ntd_capsid/1'>NTD </scene> (in green) and <scene name='71/719864/Ctd/2'>CTD </scene> (in yellow). These two domains are linked together thanks to a <scene name='71/719864/Flexible_linker/2'>Flexible linker </scene> (in orange). <ref name="C"/>

	=== Tertiary structure ===		=== Tertiary structure ===
Line 40:		Line 40:
	NTD forms both hexameric or pentameric rings, while CTD forms symmetric homodimers which connect the rings into a hexagonal lattice. Moreover, the formation of hexamers and pentamers is controlled by an electrostatic switch, thanks to this process, hexamers are favored compared to pentamers. Pentamer and hexamer structures are very close to each other, in either case, the CTDs form a belt which encircles the inner ring of NTDs.		NTD forms both hexameric or pentameric rings, while CTD forms symmetric homodimers which connect the rings into a hexagonal lattice. Moreover, the formation of hexamers and pentamers is controlled by an electrostatic switch, thanks to this process, hexamers are favored compared to pentamers. Pentamer and hexamer structures are very close to each other, in either case, the CTDs form a belt which encircles the inner ring of NTDs.
	Intermolecular NTD-NTD contacts facilitate the formation of the NTD rings, while NTD-CTD contacts maintain the CTD subunits in the belts. There is no intramolecular interaction between the NTD and CTD of each subunit, except the peptidic linkage between these two domains of course. Furthermore, the flexible linker is able to adopt different conformations, which is very useful because the monomers can position themselves in an optimal manner to permit the interaction surfaces in pentamer and hexamer. NTD rings form a rigid structure, this is not the case of CTDs in belts which are mobile and able to rotate, relative to the NTD ring. CTD pivotes such as a rigid body about four intermolecular helix-capping hydrogen bounds at the NTD-CTD interface.		Intermolecular NTD-NTD contacts facilitate the formation of the NTD rings, while NTD-CTD contacts maintain the CTD subunits in the belts. There is no intramolecular interaction between the NTD and CTD of each subunit, except the peptidic linkage between these two domains of course. Furthermore, the flexible linker is able to adopt different conformations, which is very useful because the monomers can position themselves in an optimal manner to permit the interaction surfaces in pentamer and hexamer. NTD rings form a rigid structure, this is not the case of CTDs in belts which are mobile and able to rotate, relative to the NTD ring. CTD pivotes such as a rigid body about four intermolecular helix-capping hydrogen bounds at the NTD-CTD interface.
-	Thus, each hexameric ring can have slightly different dihedral angles relative to its adjacent rings thanks to the CTDs movments. NTD rings interactions are possible thanks to the first three α-helices of each subunit, they forme a 15-helix barrel in the pentamer and a 18-helix barrel in the hexamer. A small hydrophobic core is located at the center of the bundle thanks to the presence of aliphatic residues, while polar sidechains are present at the periphery and do hydrophilic interactions.	+	Thus, each hexameric ring can have slightly different dihedral angles relative to its adjacent rings thanks to the CTDs movments. NTD rings interactions are possible thanks to the first three α-helices of each subunit, they forme a 15-helix barrel in the pentamer and a 18-helix barrel in the hexamer. A small hydrophobic core is located at the center of the bundle thanks to the presence of aliphatic residues, while polar sidechains are present at the periphery and do hydrophilic interactions. <ref name="B"/> <ref>[http://www.ncbi.nlm.nih.gov/pubmed/?term=nature09640 Nature. 2011 Jan 20;469(7330):424-7. doi: 10.1038/nature09640. Atomic-level modelling of the HIV capsid. Pornillos O, Ganser-Pornillos BK, Yeager M.] </ref>
-	~~[2]~~ <ref name="B"/>	+

Loïc Duffet at 12:40, 29 January 2016

Loïc Duffet — Fri, 29 Jan 2016 12:40:12 GMT

←Older revision		Revision as of 12:40, 29 January 2016
Line 20:		Line 20:
	=== Structural basis of HIV-1 mature capsid ===		=== Structural basis of HIV-1 mature capsid ===

-	Each HIV-1 virus owns a '''conical core capsid''' that encapsulates the ssRNA(+) viral genome and some viral enzymes that are essential for the host infection. This capsid contains '''about 250 hexamers and 12 pentamers of the CA protein''', pentamers are important to generate the curvature of the structure. This capsid is the mature capsid, its formation results in the maturation and disassembly of the immature gag polyproteins (first structural protein products which are encoded by the HIV-1 genome) by viral proteases. CA proteins are organized in '''two domains''': an N-terminal domain ( <scene name='71/719864/Ntd_capsid/1'>NTD </scene>) and a C-terminal domain (<scene name='71/719864/Ctd/2'>CTD </scene>). The mature capsid is formed by the assembly of approximately two-thirds of the mature CA proteins in the viral particle. CA proteins bind together and organize themselves in order to create a '''lattice of hexameric rings''', these rings contain an '''inner ring of six <scene name='71/719864/Ntd_capsid/1'>NTD </scene>s''', surrounded by a '''belt of six <scene name='71/719864/Ctd/2'>CTD </scene>s'''. Then, 12 CA pentamers join the structure, it permits the formation of a closed protein shell. <ref name="C">	+	Each HIV-1 virus owns a '''conical core capsid''' that encapsulates the ssRNA(+) viral genome and some viral enzymes that are essential for the host infection. This capsid contains '''about 250 hexamers and 12 pentamers of the CA protein''', pentamers are important to generate the curvature of the structure. This capsid is the mature capsid, its formation results in the maturation and disassembly of the immature gag polyproteins (first structural protein products which are encoded by the HIV-1 genome) by viral proteases. CA proteins are organized in '''two domains''': an N-terminal domain ( <scene name='71/719864/Ntd_capsid/1'>NTD </scene>) and a C-terminal domain (<scene name='71/719864/Ctd/2'>CTD </scene>). The mature capsid is formed by the assembly of approximately two-thirds of the mature CA proteins in the viral particle. CA proteins bind together and organize themselves in order to create a '''lattice of hexameric rings''', these rings contain an '''inner ring of six <scene name='71/719864/Ntd_capsid/1'>NTD </scene>s''', surrounded by a '''belt of six <scene name='71/719864/Ctd/2'>CTD </scene>s'''. Then, 12 CA pentamers join the structure, it permits the formation of a closed protein shell. <ref name="C"/>

	[[Image:capsid.jpg]]		[[Image:capsid.jpg]]
Line 26:		Line 26:
	=== Primary structure ===		=== Primary structure ===

-	CA proteins are composed of '''about 230 residues''' [4] and as we mentioned above they contain two domains: <scene name='71/719864/Ntd_capsid/1'>NTD </scene> (in green) and <scene name='71/719864/Ctd/2'>CTD </scene> (in yellow). These two domains are linked together thanks to a <scene name='71/719864/Flexible_linker/2'>Flexible linker </scene> (in orange). <ref name="C">	+	CA proteins are composed of '''about 230 residues''' [4] and as we mentioned above they contain two domains: <scene name='71/719864/Ntd_capsid/1'>NTD </scene> (in green) and <scene name='71/719864/Ctd/2'>CTD </scene> (in yellow). These two domains are linked together thanks to a <scene name='71/719864/Flexible_linker/2'>Flexible linker </scene> (in orange). <ref name="C"/>

	=== Tertiary structure ===		=== Tertiary structure ===
Line 41:		Line 41:
	Intermolecular NTD-NTD contacts facilitate the formation of the NTD rings, while NTD-CTD contacts maintain the CTD subunits in the belts. There is no intramolecular interaction between the NTD and CTD of each subunit, except the peptidic linkage between these two domains of course. Furthermore, the flexible linker is able to adopt different conformations, which is very useful because the monomers can position themselves in an optimal manner to permit the interaction surfaces in pentamer and hexamer. NTD rings form a rigid structure, this is not the case of CTDs in belts which are mobile and able to rotate, relative to the NTD ring. CTD pivotes such as a rigid body about four intermolecular helix-capping hydrogen bounds at the NTD-CTD interface.		Intermolecular NTD-NTD contacts facilitate the formation of the NTD rings, while NTD-CTD contacts maintain the CTD subunits in the belts. There is no intramolecular interaction between the NTD and CTD of each subunit, except the peptidic linkage between these two domains of course. Furthermore, the flexible linker is able to adopt different conformations, which is very useful because the monomers can position themselves in an optimal manner to permit the interaction surfaces in pentamer and hexamer. NTD rings form a rigid structure, this is not the case of CTDs in belts which are mobile and able to rotate, relative to the NTD ring. CTD pivotes such as a rigid body about four intermolecular helix-capping hydrogen bounds at the NTD-CTD interface.
	Thus, each hexameric ring can have slightly different dihedral angles relative to its adjacent rings thanks to the CTDs movments. NTD rings interactions are possible thanks to the first three α-helices of each subunit, they forme a 15-helix barrel in the pentamer and a 18-helix barrel in the hexamer. A small hydrophobic core is located at the center of the bundle thanks to the presence of aliphatic residues, while polar sidechains are present at the periphery and do hydrophilic interactions.		Thus, each hexameric ring can have slightly different dihedral angles relative to its adjacent rings thanks to the CTDs movments. NTD rings interactions are possible thanks to the first three α-helices of each subunit, they forme a 15-helix barrel in the pentamer and a 18-helix barrel in the hexamer. A small hydrophobic core is located at the center of the bundle thanks to the presence of aliphatic residues, while polar sidechains are present at the periphery and do hydrophilic interactions.
-	[2] <ref name="B">	+	[2] <ref name="B"/>

Loïc Duffet at 12:38, 29 January 2016

Loïc Duffet — Fri, 29 Jan 2016 12:38:20 GMT

←Older revision		Revision as of 12:38, 29 January 2016
Line 35:		Line 35:
	=== Quaternary structure ===		=== Quaternary structure ===

-	CA hexamers formation is due to intermolecular highly cooperative and noncovalent interactions, between the NTD of one subunit and the CTD of the neighbouring subunit within the same hexameric ring. These NTD-CTD interactions are crucial for the HIV-1 capsid assembly. CTD-CTD contacts and NTD-NTD contacts also exist for CA hexamers and pentamers formation. <ref name="C">[http://www.ncbi.nlm.nih.gov/pubmed/?term=%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BCStructural+basis+of+HIV-1+capsid+recognition+by+PF74+and+CPSF6 Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18625-30. doi: 10.1073/pnas.1419945112. Epub 2014 Dec 17.	+	CA hexamers formation is due to intermolecular highly cooperative and noncovalent interactions, between the NTD of one subunit and the CTD of the neighbouring subunit within the same hexameric ring. These NTD-CTD interactions are crucial for the HIV-1 capsid assembly. CTD-CTD contacts and NTD-NTD contacts also exist for CA hexamers and pentamers formation. <ref name="C">[http://www.ncbi.nlm.nih.gov/pubmed/?term=%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BCStructural+basis+of+HIV-1+capsid+recognition+by+PF74+and+CPSF6 Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18625-30. doi: 10.1073/pnas.1419945112. Epub 2014 Dec 17.
-	Structural basis of HIV-1 capsid recognition by PF74 and CPSF6.	+	Structural basis of HIV-1 capsid recognition by PF74 and CPSF6. Bhattacharya A, Alam SL, Fricke T, Zadrozny K, Sedzicki J, Taylor AB, Demeler B, Pornillos O, Ganser-Pornillos BK, Diaz-Griffero F, Ivanov DN, Yeager M.] </ref>
-	Bhattacharya A, Alam SL, Fricke T, Zadrozny K, Sedzicki J, Taylor AB, Demeler B, Pornillos O, Ganser-Pornillos BK, Diaz-Griffero F, Ivanov DN, Yeager M.] </ref>	+

	NTD forms both hexameric or pentameric rings, while CTD forms symmetric homodimers which connect the rings into a hexagonal lattice. Moreover, the formation of hexamers and pentamers is controlled by an electrostatic switch, thanks to this process, hexamers are favored compared to pentamers. Pentamer and hexamer structures are very close to each other, in either case, the CTDs form a belt which encircles the inner ring of NTDs.		NTD forms both hexameric or pentameric rings, while CTD forms symmetric homodimers which connect the rings into a hexagonal lattice. Moreover, the formation of hexamers and pentamers is controlled by an electrostatic switch, thanks to this process, hexamers are favored compared to pentamers. Pentamer and hexamer structures are very close to each other, in either case, the CTDs form a belt which encircles the inner ring of NTDs.

Loïc Duffet at 12:36, 29 January 2016

Loïc Duffet — Fri, 29 Jan 2016 12:36:19 GMT

←Older revision		Revision as of 12:36, 29 January 2016
Line 50:		Line 50:

	You can find bellow in a non exhaustive list of p24 partners :		You can find bellow in a non exhaustive list of p24 partners :
-	* Cytoskeleton (MAP1A, MAP1S, CKAP1, WIRE).<ref>[http://retrovirology.biomedcentral.com/articles/10.1186/1742-4690-10-S1-P34 Fernandez J, Gärtner K, Becker A, et al. HIV-1 capsid interacts with cytoskeletal-associated proteins for intracytoplasmic routing to the nucleus. Retrovirology. 2013;10(Suppl 1):P34. doi:10.1186/1742-4690-10-S1-P34.]</ref> <ref>[http://www.ncbi.nlm.nih.gov/pubmed/25505242 Fernandez J, Portilho DM, Danckaert A, Munier S, Becker A, Roux P, Zambo A, Shorte S, Jacob Y, Vidalain PO, Charneau P, Clavel F, Arhel NJ. Microtubule-associated proteins 1 (MAP1) promote human immunodeficiency virus type I (HIV-1) intracytoplasmic routing to the nucleus. J Biol Chem. 2015 Feb 20;290(8):4631-46. doi: 10.1074/jbc.M114.613133. Epub 2014 Dec 11.]</ref>	+	* Cytoskeleton (MAP1A, MAP1S, CKAP1, WIRE).<ref>[http://retrovirology.biomedcentral.com/articles/10.1186/1742-4690-10-S1-P34 Fernandez J, Gärtner K, Becker A, et al. HIV-1 capsid interacts with cytoskeletal-associated proteins for intracytoplasmic routing to the nucleus. Retrovirology. 2013;10(Suppl 1):P34. doi:10.1186/1742-4690-10-S1-P34.]</ref> <ref>[http://www.ncbi.nlm.nih.gov/pubmed/25505242 Fernandez J, Portilho DM, Danckaert A, Munier S, Becker A, Roux P, Zambo A, Shorte S, Jacob Y, Vidalain PO, Charneau P, Clavel F, Arhel NJ. Microtubule-associated proteins 1 (MAP1) promote human immunodeficiency virus type I (HIV-1) intracytoplasmic routing to the nucleus. J Biol Chem. 2015 Feb 20;290(8):4631-46. doi: 10.1074/jbc.M114.613133. Epub 2014 Dec 11.] </ref>

	* Cyclophylin A <ref>[http://jvi.asm.org/content/84/10/5181.long Marisa S. Briones, Charles W. Dobard and Samson A. Chow. Role of Human Immunodeficiency Virus Type 1 Integrase in Uncoating of the Viral Core. Accepted manuscript posted online 10 March 2010, doi:.1128/JVI.02382-09		* Cyclophylin A <ref>[http://jvi.asm.org/content/84/10/5181.long Marisa S. Briones, Charles W. Dobard and Samson A. Chow. Role of Human Immunodeficiency Virus Type 1 Integrase in Uncoating of the Viral Core. Accepted manuscript posted online 10 March 2010, doi:.1128/JVI.02382-09

Loïc Duffet at 12:33, 29 January 2016

Loïc Duffet — Fri, 29 Jan 2016 12:33:53 GMT

←Older revision		Revision as of 12:33, 29 January 2016
Line 20:		Line 20:
	=== Structural basis of HIV-1 mature capsid ===		=== Structural basis of HIV-1 mature capsid ===

-	Each HIV-1 virus owns a '''conical core capsid''' that encapsulates the ssRNA(+) viral genome and some viral enzymes that are essential for the host infection. This capsid contains '''about 250 hexamers and 12 pentamers of the CA protein''', pentamers are important to generate the curvature of the structure. This capsid is the mature capsid, its formation results in the maturation and disassembly of the immature gag polyproteins (first structural protein products which are encoded by the HIV-1 genome) by viral proteases. CA proteins are organized in '''two domains''': an N-terminal domain ( <scene name='71/719864/Ntd_capsid/1'>NTD </scene>) and a C-terminal domain (<scene name='71/719864/Ctd/2'>CTD </scene>). The mature capsid is formed by the assembly of approximately two-thirds of the mature CA proteins in the viral particle. CA proteins bind together and organize themselves in order to create a '''lattice of hexameric rings''', these rings contain an '''inner ring of six <scene name='71/719864/Ntd_capsid/1'>NTD </scene>s''', surrounded by a '''belt of six <scene name='71/719864/Ctd/2'>CTD </scene>s'''. Then, 12 CA pentamers join the structure, it permits the formation of a closed protein shell. ~~[1]~~	+	Each HIV-1 virus owns a '''conical core capsid''' that encapsulates the ssRNA(+) viral genome and some viral enzymes that are essential for the host infection. This capsid contains '''about 250 hexamers and 12 pentamers of the CA protein''', pentamers are important to generate the curvature of the structure. This capsid is the mature capsid, its formation results in the maturation and disassembly of the immature gag polyproteins (first structural protein products which are encoded by the HIV-1 genome) by viral proteases. CA proteins are organized in '''two domains''': an N-terminal domain ( <scene name='71/719864/Ntd_capsid/1'>NTD </scene>) and a C-terminal domain (<scene name='71/719864/Ctd/2'>CTD </scene>). The mature capsid is formed by the assembly of approximately two-thirds of the mature CA proteins in the viral particle. CA proteins bind together and organize themselves in order to create a '''lattice of hexameric rings''', these rings contain an '''inner ring of six <scene name='71/719864/Ntd_capsid/1'>NTD </scene>s''', surrounded by a '''belt of six <scene name='71/719864/Ctd/2'>CTD </scene>s'''. Then, 12 CA pentamers join the structure, it permits the formation of a closed protein shell. <ref name="C">

	[[Image:capsid.jpg]]		[[Image:capsid.jpg]]
Line 26:		Line 26:
	=== Primary structure ===		=== Primary structure ===

-	CA proteins are composed of '''about 230 residues''' [4] and as we mentioned above they contain two domains: <scene name='71/719864/Ntd_capsid/1'>NTD </scene> (in green) and <scene name='71/719864/Ctd/2'>CTD </scene> (in yellow). These two domains are linked together thanks to a <scene name='71/719864/Flexible_linker/2'>Flexible linker </scene> (in orange). ~~[1]~~	+	CA proteins are composed of '''about 230 residues''' [4] and as we mentioned above they contain two domains: <scene name='71/719864/Ntd_capsid/1'>NTD </scene> (in green) and <scene name='71/719864/Ctd/2'>CTD </scene> (in yellow). These two domains are linked together thanks to a <scene name='71/719864/Flexible_linker/2'>Flexible linker </scene> (in orange). <ref name="C">

	=== Tertiary structure ===		=== Tertiary structure ===

	CA tertiary protein structure is composed of '''seven helices in the NTD domain and eight helices in the CTD domain'''. The conserved tertiary structures take different quaternary arrangement during the new viral particle assembly. <ref name="B">[http://www.ncbi.nlm.nih.gov/pubmed/?term=Structure+of+the+imma+%CC%8Ature+HIV-1+capsid+in+intact+virus+particles+at+8.8+A+resolution Nature. 2015 Jan 22;517(7535):505-8. doi: 10.1038/nature13838. Epub 2014 Nov 2. Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution.		CA tertiary protein structure is composed of '''seven helices in the NTD domain and eight helices in the CTD domain'''. The conserved tertiary structures take different quaternary arrangement during the new viral particle assembly. <ref name="B">[http://www.ncbi.nlm.nih.gov/pubmed/?term=Structure+of+the+imma+%CC%8Ature+HIV-1+capsid+in+intact+virus+particles+at+8.8+A+resolution Nature. 2015 Jan 22;517(7535):505-8. doi: 10.1038/nature13838. Epub 2014 Nov 2. Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution.
-	Schur ~~FK1~~, Hagen ~~WJ2~~, Rumlová M3, Ruml T4, Müller B5, Kräusslich ~~HG5~~, Briggs ~~JA1~~]</ref>	+	Schur FK, Hagen WJ, Rumlová M, Ruml T, Müller B, Kräusslich HG, Briggs JA]</ref>
		+
		+	=== Quaternary structure ===
		+
		+	CA hexamers formation is due to intermolecular highly cooperative and noncovalent interactions, between the NTD of one subunit and the CTD of the neighbouring subunit within the same hexameric ring. These NTD-CTD interactions are crucial for the HIV-1 capsid assembly. CTD-CTD contacts and NTD-NTD contacts also exist for CA hexamers and pentamers formation. <ref name="C">[http://www.ncbi.nlm.nih.gov/pubmed/?term=%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BC%EF%BF%BCStructural+basis+of+HIV-1+capsid+recognition+by+PF74+and+CPSF6 Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18625-30. doi: 10.1073/pnas.1419945112. Epub 2014 Dec 17.
		+	Structural basis of HIV-1 capsid recognition by PF74 and CPSF6.
		+	Bhattacharya A, Alam SL, Fricke T, Zadrozny K, Sedzicki J, Taylor AB, Demeler B, Pornillos O, Ganser-Pornillos BK, Diaz-Griffero F, Ivanov DN, Yeager M.] </ref>
		+
		+	NTD forms both hexameric or pentameric rings, while CTD forms symmetric homodimers which connect the rings into a hexagonal lattice. Moreover, the formation of hexamers and pentamers is controlled by an electrostatic switch, thanks to this process, hexamers are favored compared to pentamers. Pentamer and hexamer structures are very close to each other, in either case, the CTDs form a belt which encircles the inner ring of NTDs.
		+	Intermolecular NTD-NTD contacts facilitate the formation of the NTD rings, while NTD-CTD contacts maintain the CTD subunits in the belts. There is no intramolecular interaction between the NTD and CTD of each subunit, except the peptidic linkage between these two domains of course. Furthermore, the flexible linker is able to adopt different conformations, which is very useful because the monomers can position themselves in an optimal manner to permit the interaction surfaces in pentamer and hexamer. NTD rings form a rigid structure, this is not the case of CTDs in belts which are mobile and able to rotate, relative to the NTD ring. CTD pivotes such as a rigid body about four intermolecular helix-capping hydrogen bounds at the NTD-CTD interface.
		+	Thus, each hexameric ring can have slightly different dihedral angles relative to its adjacent rings thanks to the CTDs movments. NTD rings interactions are possible thanks to the first three α-helices of each subunit, they forme a 15-helix barrel in the pentamer and a 18-helix barrel in the hexamer. A small hydrophobic core is located at the center of the bundle thanks to the presence of aliphatic residues, while polar sidechains are present at the periphery and do hydrophilic interactions.
		+	[2] <ref name="B">
		+

	== Interactions with others partners ==		== Interactions with others partners ==