User:Matthew Chien/Sandbox 1: Difference between revisions

C1q is observed to have many active sites depending on what it is interacting with, with most of these active sites being located on the globular head regions. The most researched interaction concerning C1q active site is its interaction with the antibody-antigen complex. C1q largely depends on ionic residues to create salt bridges and ionic bonds with the Cγ2 domain of IgG or the Cμ3 domain of IgM. The Cγ2 of IgG is located on the Fc region, which becomes aggregated upon complexing with antigens, allowing for increased affinity to C1q. <scene name='10/1078778/Gc1q_active_site_1/1'>Residues</scene> Glu198 -X- Asp200 -X- Lys202 on the A chain of the C1q globular head have been shown to be a consistent active site motif on C1q. This region forms an <scene name='10/1078778/Anti-parallel_beta_sheet/1'>antiparallel ß-sheet</scene>, promoting stability. Another active site has been observed on the B chain of the globular head region (ghB) at <scene name='10/1078778/114_129_c1q_active_site/1'>residues</scene> 114-129. The principle residues involved in binding are the Arg114 and Arg129. These residues interact with negatively charged residues on IgG, mostly Asp and Glu, such as residues Glu195 and Glu287. A common motif seen on IgG that these active sites interact with is Glu - X - Lys - X - Lys, located at residues 318, 320, and 322 respectively. This is a common motif seen on many proteins associated with the immune system, which enforces the observation that C1q can interact with many different proteins in many different contexts. One study showed that an arginine or lysine is required at positions 320 and 322 and a glutamic acid or threonine is required at position 318 in order for C1q to successfully bind. This suggests that a hydrogen bond at position 318 and an ionic interaction at positions 320 and 322 are required for C1q to bind to IgG and other epitopes. <ref>PMID:8486696</ref><ref>PMID:3258649</ref>