title: Crystal structure of trimeric carbohydrate recognition and neck domains of surfactant protein A.
abstract: Surfactant protein A (SP-A), one of four proteins associated with pulmonary surfactant, binds with high affinity to alveolar phospholipid membranes, positioning the protein at the first line of defense against inhaled pathogens. SP-A exhibits both calcium-dependent carbohydrate binding, a characteristic of the collectin family, and specific interactions with lipid membrane components. The crystal structure of the trimeric carbohydrate recognition domain and neck domain of SP-A was solved to 2.1-A resolution with multiwavelength anomalous dispersion phasing from samarium. Two metal binding sites were identified, one in the highly conserved lectin site and the other 8.5 A away. The interdomain carbohydrate recognition domain-neck angle is significantly less in SP-A than in the homologous collectins, surfactant protein D, and mannose-binding protein. This conformational difference may endow the SP-A trimer with a more extensive hydrophobic surface capable of binding lipophilic membrane components. The appearance of this surface suggests a putative binding region for membrane-derived SP-A ligands such as phosphatidylcholine and lipid A, the endotoxic lipid component of bacterial lipopolysaccharide that mediates the potentially lethal effects of Gram-negative bacterial infection.
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Head
authors.forename: Tanya R
authors.initials: TR
authors.lastname: Mealy
authors.forename: Francis X
authors.initials: FX
authors.lastname: McCormack
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Seaton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D008024:Ligands; D008051:Lipid Bilayers / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D037662:Pulmonary Surfactant-Associated Protein A / Q000737:chemistry*; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry; D051381:Rats; D012493:Samarium / Q000494:pharmacology
chemical_list: D008024:Ligands; D008051:Lipid Bilayers; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D012493:Samarium