Crystal structure of the trimeric alpha-helical coiled-coil and the three lectin domains of human lung surfactant protein D

Background: Human lung surfactant protein D (hSP-D) belongs to the collecti n family of C-type lectins and participates in the innate immune surveillan ce against microorganisms in the lung through recognition of carbohydrate l igands present on the surface of pathogens. The involvement of this protein in innate immunity and the allergic response make it the subject of much i nterest. Results: We have determined the crystal structure of a trimeric fragment of hSP-D at 2.3 Angstrom resolution. The structure comprises an alpha-helical coiled-coil and three carbohydrate-recognition domains (CRDs). An interest ing deviation from symmetry was found in the projection of a single tyrosin e sidechain into the centre of the coiled-coil; the asymmetry of this resid ue influences the orientation of one of the adjacent CRDs. The deft between the three CRDs presents a large positively charged surface. Conclusions: The fold of the CRD of hSP-D is similar to that of the mannan- binding protein (MBP), but its orientation relative to the alpha-helical co iled-coil region differs somewhat to that seen in the MBP structure. The no vel central packing of the tyrosine sidechain within the coiled-coil and th e resulting asymmetric orientation of the CRDs has unexpected functional im plications. The positively charged surface might facilitate binding to nega tively charged structures, such as lipopolysaccharides.