Crystal structure of trimeric carbohydrate recognition and neck domains of surfactant protein A.
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.
Head
James F
JF
Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Mealy
Tanya R
TR
McCormack
Francis X
FX
Seaton
Barbara A
BA
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
D008024:Ligands; D008051:Lipid Bilayers; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D012493:Samarium