5FFR

Crystal Structure of Surfactant Protein-A complexed with phosphocholine

5FFR の概要

• エントリーDOI: 10.2210/pdb5ffr/pdb
• 関連するPDBエントリー: 5FFS 5FFT
• 分子名称: Pulmonary surfactant-associated protein A, CALCIUM ION, PHOSPHOCHOLINE, ... (5 entities in total)
• 機能のキーワード: collectin, carbohydrate binding, lectin, lipid binding, sugar binding protein
• 由来する生物種: Rattus norvegicus (Rat)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16951.80

構造登録者

Goh, B.C.,Wu, H.,Rynkiewicz, M.J.,Schulten, K.,Seaton, B.A.,McCormack, F.X. (登録日: 2015-12-18, 公開日: 2016-07-06, 最終更新日: 2025-04-02)

主引用文献

Goh, B.C.,Wu, H.,Rynkiewicz, M.J.,Schulten, K.,Seaton, B.A.,McCormack, F.X.
Elucidation of Lipid Binding Sites on Lung Surfactant Protein A Using X-ray Crystallography, Mutagenesis, and Molecular Dynamics Simulations.
Biochemistry, 55:3692-3701, 2016

PubMed 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-π 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.

PubMed: 27324153
DOI: 10.1021/acs.biochem.6b00048

実験手法

X-RAY DIFFRACTION (2.2 Å)