Department of Physiology and Biophysics, Boston University School of Medicine, Massachusetts, USA.
Innate Immun. 2010 Jun;16(3):143-50. doi: 10.1177/1753425910368716. Epub 2010 Apr 27.
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.
肺表面活性物质蛋白 A（SP-A）和 D（SP-D）的宿主防御作用最初是在 20 世纪 80 年代被怀疑的，当时分子特征表明它们与血清急性期反应物甘露糖结合凝集素有序列同源性。此后，SP-A 和 SP-D 已被证明在先天免疫和肺稳态中发挥着多样且重要的作用。它们在表面活性物质中的位置使其能够与肺泡病原体相互作用。尽管具有广泛的结构相似性，但这两种蛋白质在与微生物表面成分、表面活性脂质和其他配体的相互作用方面表现出许多功能差异和显著的差异。最近的晶体学研究为这些观察到的差异提供了许多新的见解。尽管这两种蛋白质都可以参与钙依赖性与糖和其他多元醇的相互作用，但它们在结合表面的空间取向、电荷和疏水性方面存在显著差异。SP-D 似乎特别适合与复杂碳水化合物和阴离子磷脂（如磷脂酰肌醇）相互作用。相比之下，SP-A 表现出与其脂质配体（包括脂质 A 和主要的表面活性脂质，二棕榈酰磷脂酰胆碱）偏好一致的特征。目前的研究表明，结构生物学方法将有助于阐明肺表面活性物质凝集素-配体识别的分子基础，并促进基于 SP-A 和 SP-D 的新型治疗方法的发展。
