title: The lectin self of complement factor H.
abstract: Complement, a part of the humoral innate immune system, is divided into three pathways. The classical and mannose-binding lectin pathways are triggered by specific recognition of foreign targets. Conversely, the alternative pathway (AP) is actively down-regulated on host tissue. Glycosaminoglycans (GAGs) and sialylated glycans mediate host recognition of the AP as self-associated molecular patterns (SAMPs) to the regulatory protein factor H (FH). This review summarizes the more recent years of research on SAMP recognition by FH from a structural biology point of view and discusses implications for two complement-associated conditions, age-related macular degeneration (AMD) and atypical hemolytic uremic syndrome (aHUS). Taking into account crystal structures that elucidated FH binding to a bacterial evasion protein and to the thioester domain of C3b, the target of FH-mediated AP restriction, a novel atomistic model for the mechanism by which FH prevents AP activation on self surfaces is proposed.
authors.affiliation: Interfaculty Institute of Biochemistry (IFIB), University of Tübingen, Hoppe-Seyler-Strasse 4, D-72076 Tübingen, Germany. Electronic address: baerbel.blaum@uni-tuebingen.de.
authors.forename: Bärbel S
authors.initials: BS
authors.lastname: Blaum
mesh_terms: D000818:Animals; D065766:Atypical Hemolytic Uremic Syndrome / Q000378:metabolism; D017242:Complement Factor H / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008268:Macular Degeneration / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism
chemical_list: D037102:Lectins; D017242:Complement Factor H; D019158:N-Acetylneuraminic Acid