title: Identification of conformational core epitope Lys⁶⁸ in C5a based on the 3-D modeling complex C5a and its functional antibody F20.
abstract: Inhibition of C5a by antibodies has been demonstrated to dramatically improve survival in various sepsis models in mice and rats. The structural basis of C5a mediated bioactivity and C5a antibody mediated neutralization are of interesting to be investigated. In the previous study, we obtained a novel functional mouse antibody named as F20. With computer-guided modeling method, the 3-D theoretical structure of F20 Fv fragment was constructed. Using the crystal structure of C5a, the 3-D complex structure of C5a and F20 Fv fragment was modeled with molecular docking method. Based on distance geometry method and intermolecular interaction theory, the key residue Lys(68) in C5a identified by F20 was predicted. The mutant experimental results showed that the residue Lys(68) was the critical residue of C5a for it's bioactivity and F20 binding activity. The present study shed new light on the structural basis of C5a mediated bioactivity. The identification of the critical residue will provide useful information for human complement C5a targeted therapeutic intervention.
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Wei
authors.forename: Zhou
authors.initials: Z
authors.lastname: Lin
authors.forename: Jiannan
authors.initials: J
authors.lastname: Feng
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.forename: Renfeng
authors.initials: R
authors.lastname: Guo
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
authors.forename: Shusheng
authors.initials: S
authors.lastname: Geng
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Lang
authors.forename: Yingxun
authors.initials: Y
authors.lastname: Sun
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D015153:Blotting, Western; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D003198:Computer Simulation; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D015936:Complement C5a