title: Preservation of antimicrobial properties of complement peptide C3a, from invertebrates to humans.
abstract: The human anaphylatoxin peptide C3a, generated during complement activation, exerts antimicrobial effects. Phylogenetic analysis, sequence analyses, and structural modeling studies paired with antimicrobial assays of peptides from known C3a sequences showed that, in particular in vertebrate C3a, crucial structural determinants governing antimicrobial activity have been conserved during the evolution of C3a. Thus, regions of the ancient C3a from Carcinoscorpius rotundicauda as well as corresponding parts of human C3a exhibited helical structures upon binding to bacterial lipopolysaccharide permeabilized liposomes and were antimicrobial against gram-negative and gram-positive bacteria. Human C3a and C4a (but not C5a) were antimicrobial, in concert with the separate evolutionary development of the chemotactic C5a. Thus, the results demonstrate that, notwithstanding a significant sequence variation, functional and structural constraints imposed on C3a during evolution have preserved critical properties governing antimicrobial activity.
authors.affiliation: Section of Dermatology and Venereology, Department of Clinical Sciences, Biomedical Center, Lund University, Tornavägen 10, SE-221 84 Lund, Sweden.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Pasupuleti
authors.forename: Björn
authors.initials: B
authors.lastname: Walse
authors.forename: Emma Andersson
authors.initials: EA
authors.lastname: Nordahl
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Martin
authors.initials: M
authors.lastname: Malmsten
authors.forename: Artur
authors.initials: A
authors.lastname: Schmidtchen
mesh_terms: D000595:Amino Acid Sequence; D000706:Anaphylatoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism; D015926:Complement C3a / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015934:Complement C4a / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015936:Complement C5a / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D006737:Horseshoe Crabs; D006801:Humans; D007448:Invertebrates; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment
chemical_list: D000706:Anaphylatoxins; D000890:Anti-Infective Agents; D015926:Complement C3a; D015934:Complement C4a; D015936:Complement C5a