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 characteri...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-10, Vol.278 (44), p.43254-43260
Main Authors: Head, James F., Mealy, Tanya R., McCormack, Francis X., Seaton, Barbara A.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
BACTERIA
Binding Sites
Carbohydrate Metabolism
CARBOHYDRATES
CRYSTAL STRUCTURE
Crystallography, X-Ray
Dimerization
INFECTIVITY
LECITHINS
LECTINS
LETHAL MUTATIONS
LIGANDS
Lipid Bilayers - metabolism
LIPIDS
LIPOPOLYSACCHARIDES
LUNGS
MATERIALS SCIENCE
MEMBRANES
Models, Molecular
Molecular Sequence Data
national synchrotron light source
PATHOGENS
PHOSPHOLIPIDS
Protein Binding
Protein Conformation
Protein Structure, Secondary
Protein Structure, Tertiary
PROTEINS
Pulmonary Surfactant-Associated Protein A - chemistry
Pulmonary Surfactant-Associated Protein D - chemistry
Rats
SAMARIUM
Samarium - pharmacology
SURFACTANTS
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Summary: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-Å resolution with multiwavelength anomalous dispersion phasing from samarium. Two metalbinding sites were identified, one in the highly conserved lectin site and the other 8.5 Å 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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M305628200