User:Matthew Chien/Sandbox 1: Difference between revisions

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C1q has been shown to partially facilitate the function of T-cells. The receptors gC1qR and cC1qR are both present on T-cells and serve as both activators and inhibitors. In the presence of immune complexes, C1q has shown to activate T-cells, acting as a bridge between the innate and adaptive immune system. In terms of inhibition, C1q is observed to suppress the activity of T-cells in certain environments to regulate the immune system and prevent autoimmune disease. C1q is known to bind to various phospholipids, namely phosphatidylserine, which is largely present on the surface of apoptotic cells. This promotes opsonization which leads to macrophage activation while also inhibiting T-cells to interact with the apoptotic cells. Over-activation of T-cells can lead to unnecessary harm within the body when their presence is not necessary and phagocytes are favored. <ref>PMID:15982298</ref><ref>PMID:20010915</ref>
C1q has been shown to partially facilitate the function of T-cells. The receptors gC1qR and cC1qR are both present on T-cells and serve as both activators and inhibitors. In the presence of immune complexes, C1q has shown to activate T-cells, acting as a bridge between the innate and adaptive immune system. In terms of inhibition, C1q is observed to suppress the activity of T-cells in certain environments to regulate the immune system and prevent autoimmune disease. C1q is known to bind to various phospholipids, namely phosphatidylserine, which is largely present on the surface of apoptotic cells. This promotes opsonization which leads to macrophage activation while also inhibiting T-cells to interact with the apoptotic cells. Over-activation of T-cells can lead to unnecessary harm within the body when their presence is not necessary and phagocytes are favored. <ref>PMID:15982298</ref><ref>PMID:20010915</ref>
== Structural Highlights ==
C1q is a 460 kDa protein complex composed of six collagen-like stems, each linked to a globular head. This produces a bouquet-like structure shown below. Each collagen-like stem is comprised of three separate chains that form a triple helix structure, totaling 18 polypeptide chains of three different types; A, B, and C. Each chain has an N-terminus in at the CLR and a <scene name='10/1078778/C-termini/1'>C-terminus</scene> at the globular head. Disulfide bonds link the N-terminus ends of A and B chains, with these dimers being linked to the C chains noncovalently. [[Image:Schematic-representation-of-structural-organization-of-human-C1q-and-of-C1-assembly-A.jpeg|thumb|right|520px|N-terminus of C1q]] These form the triple helices that attach to the globular head, making the bouquet-like structure. The globular heads are comprised of three independently folding domains, making them heterotrimeric. The globular heads are very compact and held together by both electrostatic and nonpolar interactions. Each globular head contains a <scene name='10/1078778/Calcium_ion/1'>calcium ion</scene>, responsible for target recognition properties and electrostatic stability. At pH 7.4, the Calcium ion is lost from the globular head, which contributes to IgG binding site recognition. <ref>PMID:23650384</ref><ref>PMID:16245926</ref>
[[Image:Frame apngframe1.png]]


== Active Site ==
== Active Site ==
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[[Image:Ijms-22-05125-g008.jpg|thumb|400px|C1q CLR active site residues Lys58 and Lys61]]
[[Image:Ijms-22-05125-g008.jpg|thumb|400px|C1q CLR active site residues Lys58 and Lys61]]
The collagen-like region (CLR) is the location of a binding site associated with a variety of non-complement related interactions, such as the binding of phagocytes to C1q as mentioned above. However, one of the most important functions of the CLR of C1q is the activation through protease of the remainder of C1; C1r and C1s. Two equivalences of C1r and C1s are bonded C1s - C1r - C1r - C1s to comprise a tetramer that, when cleaved after the bonding of C1q to an epitope, activates the classical pathway of complement activity, promoting inflammation and phagocytosis. The active site on the CLR of C1q is proposed to be lysine residues located at position 61 on the B chain and position 58 on the A chain. These basic residues create salt bridges with associated residues on C1r, generally a glutamic acid or aspartic acid. These residues are coordinated with the Ca2+ ion present in C1q through single carboxyl oxygens, which is available for mediating through an electrostatic bond with a basic residue. Through activation, the C1r - C1r bond is broken, which induces conformational changes in C1r that subsequently cleaves C1s. <ref>PMID:29311313</ref><ref>PMID:23922389</ref><ref>PMID:1939090</ref><ref>PMID:34066122</ref>
The collagen-like region (CLR) is the location of a binding site associated with a variety of non-complement related interactions, such as the binding of phagocytes to C1q as mentioned above. However, one of the most important functions of the CLR of C1q is the activation through protease of the remainder of C1; C1r and C1s. Two equivalences of C1r and C1s are bonded C1s - C1r - C1r - C1s to comprise a tetramer that, when cleaved after the bonding of C1q to an epitope, activates the classical pathway of complement activity, promoting inflammation and phagocytosis. The active site on the CLR of C1q is proposed to be lysine residues located at position 61 on the B chain and position 58 on the A chain. These basic residues create salt bridges with associated residues on C1r, generally a glutamic acid or aspartic acid. These residues are coordinated with the Ca2+ ion present in C1q through single carboxyl oxygens, which is available for mediating through an electrostatic bond with a basic residue. Through activation, the C1r - C1r bond is broken, which induces conformational changes in C1r that subsequently cleaves C1s. <ref>PMID:29311313</ref><ref>PMID:23922389</ref><ref>PMID:1939090</ref><ref>PMID:34066122</ref>
== Structural Highlights ==
C1q is a 460 kDa protein complex composed of six collagen-like stems, each linked to a globular head. This produces a bouquet-like structure shown below. Each collagen-like stem is comprised of three separate chains that form a triple helix structure, totaling 18 polypeptide chains of three different types; A, B, and C. Each chain has an N-terminus in at the CLR and a <scene name='10/1078778/C-termini/1'>C-terminus</scene> at the globular head. Disulfide bonds link the N-terminus ends of A and B chains, with these dimers being linked to the C chains noncovalently. [[Image:Schematic-representation-of-structural-organization-of-human-C1q-and-of-C1-assembly-A.jpeg|thumb|right|520px|N-terminus of C1q]] These form the triple helices that attach to the globular head, making the bouquet-like structure. The globular heads are comprised of three independently folding domains, making them heterotrimeric. The globular heads are very compact and held together by both electrostatic and nonpolar interactions. Each globular head contains a <scene name='10/1078778/Calcium_ion/1'>calcium ion</scene>, responsible for target recognition properties and electrostatic stability. At pH 7.4, the Calcium ion is lost from the globular head, which contributes to IgG binding site recognition. <ref>PMID:23650384</ref><ref>PMID:16245926</ref>
[[Image:Frame apngframe1.png]]


== Disease ==
== Disease ==
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