Structural insights into the recognition properties of human ficolins.
Innate immunity relies upon the ability of a variety of recognition molecules to sense pathogens through conserved molecular signatures that are often carbohydrates. Ficolins are oligomeric proteins assembled from collagen-like stalks and fibrinogen-like domains that have the ability to sense these molecular patterns on both pathogens and apoptotic cell surfaces. Three ficolins, termed L, H and M, have been identified in humans. They differ in their localization and concentration in extracellular fluids, their mode of secretion and their recognition properties. From a structural point of view, ficolins are assembled from basal trimeric subunits comprising a collagen-like triple helix and a globular domain composed of 3 fibrinogen-like domains. The globular domains are responsible for sensing danger signals whereas the collagen-like stalks provide a link with immune effectors. This review mainly focuses on the structure and recognition properties of the 3 human ficolins, as revealed by recent crystallographic analysis of their recognition domains. The ligand binding sites have been identified in the 3 ficolins and their recognition mechanisms have been characterized at the atomic level. In the case of M-ficolin, a structural transition at acidic pH disables the binding pocket, and thus likely participates in the functional cycle of this protein.
Garlatti
Virginie
V
Institut de Biologie Structurale JP Ebel, Grenoble, France.
Martin
Lydie
L
Lacroix
Monique
M
Gout
Evelyne
E
Arlaud
Gérard J
GJ
Thielens
Nicole M
NM
Gaboriaud
Christine
C
D002241:Carbohydrates / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D037102:Lectins / Q000737:chemistry / Q000276:immunology*; D019158:N-Acetylneuraminic Acid / Q000276:immunology; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D051192:Receptors, Pattern Recognition / Q000276:immunology; D000097604:Ficolins
D002241:Carbohydrates; D003165:Complement System Proteins; D037102:Lectins; D019158:N-Acetylneuraminic Acid; D051192:Receptors, Pattern Recognition; D000097604:Ficolins