Unknown

Dataset Information

0

Elucidation of Lipid Binding Sites on Lung Surfactant Protein A Using X-ray Crystallography, Mutagenesis, and Molecular Dynamics Simulations.


ABSTRACT: Surfactant protein A (SP-A) is a collagenous C-type lectin (collectin) that is critical for pulmonary defense against inhaled microorganisms. Bifunctional avidity of SP-A for pathogen-associated molecular patterns (PAMPs) such as lipid A and for dipalmitoylphosphatidylcholine (DPPC), the major component of surfactant membranes lining the air-liquid interface of the lung, ensures that the protein is poised for first-line interactions with inhaled pathogens. To improve our understanding of the motifs that are required for interactions with microbes and surfactant structures, we explored the role of the tyrosine-rich binding surface on the carbohydrate recognition domain of SP-A in the interaction with DPPC and lipid A using crystallography, site-directed mutagenesis, and molecular dynamics simulations. Critical binding features for DPPC binding include a three-walled tyrosine cage that binds the choline headgroup through cation-? interactions and a positively charged cluster that binds the phosphoryl group. This basic cluster is also critical for binding of lipid A, a bacterial PAMP and target for SP-A. Molecular dynamics simulations further predict that SP-A binds lipid A more tightly than DPPC. These results suggest that the differential binding properties of SP-A favor transfer of the protein from surfactant DPPC to pathogen membranes containing appropriate lipid PAMPs to effect key host defense functions.

SUBMITTER: Goh BC 

PROVIDER: S-EPMC5663190 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Elucidation of Lipid Binding Sites on Lung Surfactant Protein A Using X-ray Crystallography, Mutagenesis, and Molecular Dynamics Simulations.

Goh Boon Chong BC   Wu Huixing H   Rynkiewicz Michael J MJ   Schulten Klaus K   Seaton Barbara A BA   McCormack Francis X FX  

Biochemistry 20160621 26


Surfactant protein A (SP-A) is a collagenous C-type lectin (collectin) that is critical for pulmonary defense against inhaled microorganisms. Bifunctional avidity of SP-A for pathogen-associated molecular patterns (PAMPs) such as lipid A and for dipalmitoylphosphatidylcholine (DPPC), the major component of surfactant membranes lining the air-liquid interface of the lung, ensures that the protein is poised for first-line interactions with inhaled pathogens. To improve our understanding of the mot  ...[more]

Similar Datasets

| S-EPMC6719169 | biostudies-literature
| S-EPMC523450 | biostudies-literature
| S-EPMC3149184 | biostudies-literature
| S-EPMC3220461 | biostudies-literature
| S-EPMC6235626 | biostudies-literature
| S-EPMC1301536 | biostudies-other
| S-EPMC5589069 | biostudies-literature
| S-EPMC5937052 | biostudies-literature
| S-EPMC7289149 | biostudies-literature
| S-EPMC7002364 | biostudies-literature