title: Review: Structural determinants of pattern recognition by lung collectins.
abstract: Host defense roles for the lung collectins, surfactant protein A (SP-A) and surfactant protein D (SP-D), were first suspected in the 1980s when molecular characterization revealed their sequence homology to the acute phase reactant of serum, mannose-binding lectin. Surfactant protein A and SP-D have since been shown to play diverse and important roles in innate immunity and pulmonary homeostasis. Their location in surfactant ideally positions them to interact with air-space pathogens. Despite extensive structural similarity, the two proteins show many functional differences and considerable divergence in their interactions with microbial surface components, surfactant lipids, and other ligands. Recent crystallographic studies have provided many new insights relating to these observed differences. Although both proteins can participate in calcium-dependent interactions with sugars and other polyols, they display significant differences in the spatial orientation, charge, and hydrophobicity of their binding surfaces. Surfactant protein D appears particularly adapted to interactions with complex carbohydrates and anionic phospholipids, such as phosphatidylinositol. By contrast, SP-A shows features consistent with its preference for lipid ligands, including lipid A and the major surfactant lipid, dipalmitoylphosphatidylcholine. Current research suggests that structural biology approaches will help to elucidate the molecular basis of pulmonary collectin-ligand recognition and facilitate development of new therapeutics based upon SP-A and SP-D.
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Massachusetts, USA. seatonba@bu.edu
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Seaton
authors.forename: Erika C
authors.initials: EC
authors.lastname: Crouch
authors.forename: Francis X
authors.initials: FX
authors.lastname: McCormack
authors.forename: James F
authors.initials: JF
authors.lastname: Head
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
authors.forename: Richard
authors.initials: R
authors.lastname: Mendelsohn
mesh_terms: D000818:Animals; D037222:Collectins / Q000276:immunology / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D011487:Protein Conformation; D051192:Receptors, Pattern Recognition
chemical_list: D037222:Collectins; D051192:Receptors, Pattern Recognition