Review: Structural determinants of pattern recognition by lung collectins

Department of Physiology and Biophysics, Boston University School of Medicine, Massachusetts, USA.
Innate Immunity (Impact Factor: 3.27). 06/2010; 16(3):143-50. DOI: 10.1177/1753425910368716
Source: PubMed


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.

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Available from: Richard Mendelsohn, Dec 23, 2013
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    • "The collectins belong to the superfamily of collagen-containing C-type lectins (hence their name), and act as pattern recognition receptors for pathogenic molecules [106,107]. Better known members include the mannan-binding lectin and the surfactant proteins A and D. There is a large body of literature documenting an innate antiviral role of these lectins, in which they neutralize viral infectivity by binding to viral fusion glycoproteins, such as influenza viral HA and NA proteins; however, their contributions in opsonizing viral antigens and triggering neutrophil oxidative respiratory burst and an inflammatory response suggest that their pharmacological potential must await a more detailed analysis of these diverse roles [96,108-112]. "
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    • "Proteins secreted by type II pneumocytes and nonciliated bronchiolar epithelium may serve various functions. While the small hydrophobic proteins SP-B and SP-C are vital for the physical properties of pulmonary surfactant and thereby lung expansion [16], [17], the hydrophilic proteins SP-A and SP-D confer innate immunity promoting phagocytosis by macrophages [18]. Furthermore, SP-A is involved in the control of surfactant production and both SP-A and SP-D have a role in limiting excessive inflammation [19], [20], [21]. "
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    • "The neck region induces polypeptide trimerization, which is further stabilized by the collagen domain. Trimers can associate to form higher-order multimeric complexes through disulfide-stabilized interactions at the N-terminus, thereby increasing binding avidity for microbes and other ligands [34]. MBL and SP-A are commonly composed of six associated trimers (octadecamers or 18-mers), which resemble a bouquet of flowers. "
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