Structural insights into the recognition properties of human ficolins

Abstract

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.