Epitope mapping for monoclonal antibodies identifies functional domains of pulmonary surfactant protein A that interact with lipids.

Kuroki, Yoshio; McCormack, F X; Ogasawara, Yoshinori; Mason, Robert J.; Voelker, Dennis R.

doi:10.1016/s0021-9258(18)43951-8

Cited by 62 publications

(24 citation statements)

References 41 publications

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“…18,19 SP-A, SP-B and SP-D are synthesized by alveolar type II cells and Clara cells, while SP-C is produced only by alveolar type II cells in normal lungs. 20 Previous reports have shown that mRNAs of SP-A and SP-C were detected in lymphnodes 21 and pleural effusion 22 from patients with lung adenocarcinoma. These evidences made us consider that the mRNAs are potential molecular markers to detect carcinoma cells in the peripheral blood.…”

Section: Discussionmentioning

confidence: 95%

Surfactant protein gene expressions for detection of lung carcinoma cells in peripheral blood

Yamamoto

Takahashi

Hirasawa

et al. 2005

Respiratory Medicine

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Section: Discussionmentioning

confidence: 95%

Surfactant protein gene expressions for detection of lung carcinoma cells in peripheral blood

Yamamoto

Takahashi

Hirasawa

et al. 2005

Respiratory Medicine

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“…Kuroki et al (42) and Ogasawara et al ( 68) created chimeras between SP-A and SP-D to define structural determinants within these two collectins, and these chimeras have proven valuable for mapping functional domains within this protein family. Swapping the four major domains (NH 2 terminus, collagen, neck, and CRD) of SP-A and SP-D implicates the neck and CRD elements of SP-A in lipid binding and inhibition of secretion in vitro.…”

Section: Sp-amentioning

confidence: 99%

“…Swapping the four major domains (NH 2 terminus, collagen, neck, and CRD) of SP-A and SP-D implicates the neck and CRD elements of SP-A in lipid binding and inhibition of secretion in vitro. The SP-A-SP-D chimeras have also facilitated the mapping of monoclonal antibody epitopes (42). One monoclonal antibody (6E3) that recognizes the neck region of SP-A blocks lipid uptake into type II cells but not lipid binding, aggregation, or inhibition of secretion in vitro.…”

Section: Sp-amentioning

confidence: 99%

Surfactant protein A and surfactant protein D in health and disease

Mason

Greene

Voelker

1998

American Journal of Physiology-Lung Cellular and Molecular Phys

151

160

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Surfactant protein (SP) A and SP-D are collagenous glycoproteins with multiple functions in the lung. Both of these proteins are calcium-dependent lectins and are structurally similar to mannose-binding protein and bovine conglutinin. Both form polyvalent multimeric structures for interactions with pathogens, cells, or other molecules. SP-A is an integral part of the surfactant system, binds phospholipids avidly, and is found in lamellar bodies and tubular myelin. Initially, most research interest focused on its role in surfactant homeostasis. Recently, more attention has been placed on the role of SP-A as a host defense molecule and its interactions with pathogens and phagocytic cells. SP-D is much less involved with the surfactant system. SP-D appears to be primarily a host defense molecule that binds surfactant phospholipids poorly and is not found in lamellar inclusion bodies or tubular myelin. Both SP-A and SP-D bind a wide spectrum of pathogens including viruses, bacteria, fungi, and pneumocystis. In addition, both molecules have been measured in the systemic circulation by immunologic methods and may be useful biomarkers of disease. The current challenges are characterization of the three-dimensional crystal structure of SP-A and SP-D, molecular cloning of their receptors, and determination of their precise physiological functions in vivo.

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“…The extent of physical overlap between these ligand binding sites is a major knowledge gap. Multiple lines of evidence have shown that the carbohydrate recognition domain (CRD) of SP-A is capable of binding to lipid. − Earlier mapping studies using chimeric SP-A proteins that contained homologous regions from surfactant protein D implicated broad domains in PC binding . The objective of this work is to refine our molecular understanding of SP-A–lipid interactions and how these features influence SP-A function.…”

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confidence: 99%

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

Goh

Rynkiewicz

et al. 2016

Biochemistry

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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 better understand 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 head group 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.

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Epitope mapping for monoclonal antibodies identifies functional domains of pulmonary surfactant protein A that interact with lipids.

Cited by 62 publications

References 41 publications

Surfactant protein gene expressions for detection of lung carcinoma cells in peripheral blood

Surfactant protein gene expressions for detection of lung carcinoma cells in peripheral blood

Surfactant protein A and surfactant protein D in health and disease

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

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