TY - JOUR
T1 - Structural determinants of pattern recognition by lung collectins
AU - Seaton, Barbara A.
AU - Crouch, Erika C.
AU - McCormack, Francis X.
AU - Head, James F.
AU - Hartshorn, Kevan L.
AU - Mendelsohn, Richard
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
KW - Lung collectins
KW - Pattern recognition
KW - SP-A
KW - SP-D
KW - X-ray crystallography
UR - http://www.scopus.com/inward/record.url?scp=77953297418&partnerID=8YFLogxK
U2 - 10.1177/1753425910368716
DO - 10.1177/1753425910368716
M3 - Review article
C2 - 20423923
AN - SCOPUS:77953297418
VL - 16
SP - 143
EP - 150
JO - Innate Immunity
JF - Innate Immunity
SN - 1753-4259
IS - 3
ER -