Sandbox Reserved 971: Difference between revisions

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==ST2/IL33 complex==
==ST2/IL33 complex==
<StructureSection load='4kc3' size='340' side='right' caption='Caption for this structure' scene=''>
<StructureSection load='4kc3' size='340' side='right' caption='Caption for this structure' scene=''>
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== Function ==
== Function ==


'''Caracteristics of IL-33:'''
===Caracteristics of IL-33===


IL-33 is constitutively expressed in several cells, such as epithelial or endothelial cells. IL-33 is also expressed in an inducible way by immune cells. In this case, the constitutive expression of IL-33 is very low or absent. In mast cells, the expression of IL-33 is induced by the calcium, but the mechanisms are still unclear. IL-33 is secreted in damaged tissues, where it activates the immune response.
IL-33 is constitutively expressed in several cells, such as epithelial or endothelial cells. IL-33 is also expressed in an inducible way by immune cells. In this case, the constitutive expression of IL-33 is very low or absent. In mast cells, the expression of IL-33 is induced by the calcium, but the mechanisms are still unclear. IL-33 is secreted in damaged tissues, where it activates the immune response.


'''Target cells:'''
===Target cells===


ST2 exists in a soluble form (sST2) and a transmembrane form (ST2L). The both forms can interact with IL-33. ST2L are expressed in T lymphocytes, when they are specializing into Th2 cells (T helper type 2 cells, a specific type of T lymphocytes). This specialization occurs in the presence of IL4, expected to be secreted by polynuclear basophils.
ST2 exists in a soluble form (sST2) and a transmembrane form (ST2L). The both forms can interact with IL-33. ST2L are expressed in T lymphocytes, when they are specializing into Th2 cells (T helper type 2 cells, a specific type of T lymphocytes). This specialization occurs in the presence of IL4, expected to be secreted by polynuclear basophils.
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== Structure ==
== Structure ==


'''Overall structure:'''
===Overall structure===


The understanding of the interaction of IL-33 with its receptors has been discovered thanks to the determination of the crystal structure of IL-33 in complex with ectodomain of ST2.  
The understanding of the interaction of IL-33 with its receptors has been discovered thanks to the determination of the crystal structure of IL-33 in complex with ectodomain of ST2.  
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The structure of IL-33 consists in a <scene name='61/614056/Beta_sheet_of_il33/2'>12 β-strands</scene> forming a β-trefoil structure. It also contains an <scene name='61/614056/Il33_alpha_helix/1'>alpha helix</scene>. Specific loops, such as the β4-β5 loop, are involved in the interaction with the accessory receptor IL-1RAcP when IL-33 is bound to ST2.
The structure of IL-33 consists in a <scene name='61/614056/Beta_sheet_of_il33/2'>12 β-strands</scene> forming a β-trefoil structure. It also contains an <scene name='61/614056/Il33_alpha_helix/1'>alpha helix</scene>. Specific loops, such as the β4-β5 loop, are involved in the interaction with the accessory receptor IL-1RAcP when IL-33 is bound to ST2.


'''IL-33/ST2 interactions:'''
===IL-33/ST2 interactions===


In the complex, IL-33 interacts with the three domains of ST2. The binding interface is very large and composed of two separate sites.  
In the complex, IL-33 interacts with the three domains of ST2. The binding interface is very large and composed of two separate sites.  


In the <scene name='61/614056/Interaction_site_1/5'>first binding site</scene>, thirteen IL-33 residues from β-loops are in contact with the D1D2 module of ST2: the four marked acids residues of IL-33 form a salt-bridge with five marked ST2 residues respectively. Besides, Glu144 and Asp149 form hydrogen bonds with main-chain atoms of ST2. IL-33 mutation of one of the acid residues (144, 148, 149 and 244) highly decreases the affinity of ST2 for IL-33.
In the <scene name='61/614056/Interaction_site_1/7'>first binding site</scene>, thirteen IL-33 residues from β-loops are in contact with the D1D2 module of ST2: the four marked acids residues of IL-33 form a salt-bridge with five marked ST2 residues respectively. Besides, Glu144 and Asp149 form hydrogen bonds with main-chain atoms of ST2. IL-33 mutation of one of the acid residues (144, 148, 149 and 244) highly decreases the affinity of ST2 for IL-33.


In the <scene name='61/614056/Interaction_site_2/2'>second binding site</scene>, eight IL-33 residues from β-strands interact with the D3 domain of ST2.  
In the <scene name='61/614056/Interaction_site_2/3'>second binding site</scene>, eight IL-33 residues from β-strands interact with the D3 domain of ST2.  


There are both hydrophobic and hydrophilic interactions. Residues of IL-33 form an hydrophobic cluster (IL-33 residues Tyr163 and Leu182 and ST2 residues Leu246, Leu306, and Leu311). A salt-bridge interaction occurs between acidic residue Glu165 and Arg313 of ST2.
There are both hydrophobic and hydrophilic interactions. Residues of IL-33 form an hydrophobic cluster (IL-33 residues Tyr163 and Leu182 and ST2 residues Leu246, Leu306, and Leu311). A salt-bridge interaction occurs between acidic residue Glu165 and Arg313 of ST2.
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