Barbara Seaton, Ph.D.

Research

The long-term research interests of our lab concern interactions between mammalian proteins and biomembranes or other large assemblies such as viruses. Our current focus is on the lung surfactant proteins A and D (SP-A and SP-D) and their role in innate defense against inhaled pathogens such as seasonal and pandemic strains of influenza A virus (IAV). These proteins are C-type lectins that can recognize sugars and other signature components on microbial surfaces, and can initiate events leading to pathogen neutralization. In our lab, we use x-ray crystallography, molecular modeling, and various biochemical and biophysical methods to understand the nature of these interactions at the highest resolution possible.

Selected Publications:

van Eijk M, Rynkiewicz MJ, White MR, Hartshorn KL, Zou X, Schulten K, Luo D, Crouch EC, Cafarella TR, Head JF, Haagsman HP, Seaton BA. (2012) A unique sugar-binding site mediates the distinct anti-influenza activity of pig surfactant protein D. J Biol Chem 287(32), 26666-77. (PMID: 22685299)

Shang FF, Rynkiewicz MJ, McCormack FX, Wu H, Cafarella TM, Head JF, Seaton BA (2011) Crystallographic complexes of surfactant protein-A and carbohydrates reveal ligand-induced conformational change. J. Biol. Chem. 286, 757-65. (PMID: 21047777)

van Eijk, M, Brunsma L, Hartshorn KL, White MR, Rynkiewicz MJ, Seaton BA, Hemrika W, Romijn RA, van Balkom BW, Haagsman HP (2011) Introduction of N-linked glycans in the lectin domain of surfactant protein D: impact on interactions with influenza A viruses. J Biol Chem 286, 20137-51. (PMID:21489996)

Crouch E, Nikolaidis N, McCormack F, McDonald B, Allen K, Rynkiewicz M, Cafarella T, White M, Lewnard K, Leymarie N, Zaia J, Seaton B, Hartshorn K (2011) Mutagenesis of SP-D informed by evolution and x-ray crystallography enhances defenses against influenza in vivo. J. Biol Chem. 286, 40681-92. (PMID: 21965658)

Seaton BA, Crouch EC, McCormack FX, Head JF, Hartshorn KL, Mendelsohn R. (2010) Structural determinants of pattern recognition by lung collectins. Innate Immun. 16: 143-150.

Crouch, E., K. Hartshorn, T. Horlacher, B. McDonald, K. Smith, T. Cafarella, B. Seaton, P. H. Seeberger, and J. Head (2009) Recognition of mannosylated ligands and influenza A virus by human surfactant protein D: contributions of an extended site and residue 343. Biochemistry 48:3335-3345

Wang H, Head J, Kosma P, Brade H, Müller-Loennies S, Sheikh S, McDonald B, Smith K, Cafarella T, Seaton B, Crou.ch E (2008) Recognition of heptoses and the inner core of bacterial lipopolysaccharides by Surfactant Protein D. Biochemistry 47,710-720.

Wang L, Brauner JW, Mao G, Crouch E, Seaton B, Head J, Smith K, Flach CR, Mendelsohn R. (2008) Interaction of recombinant surfactant protein D with lipopolysaccharide: conformation and orientation of bound protein by IRRAS and simulations. Biochemistry 47, 8103-8113.

Crouch, E.C., McDonald, B., Smith, K., Mealy (Carafella), T., Seaton, B.A., Head, J.F. (2007) Critical Role of Arg/Lys343 in the Species-Dependent Recognition of Phosphatidylinositol by Pulmonary Surfactant Protein D. Biochemistry 46, 5160-5169.

Crouch, E.C., McDonald, B., Smith, K., (Mealy) Cafarella, T., Seaton, B.A., Head, J.F. (2006) Contributions of Phe335 to Carbohydrate Recognition by Human Surfactant Protein D: Stacking Interactions with Lung Collectin Ligands. J. Biol. Chem. 281, 18008-14.

Crouch, E.C., Smith, K , McDonald, B., Briner, D., Linders, B., McDonald, J., Holmskov, U., Head, J.F., Hartshorn, K. (2006) Species differences in the carbohydrate binding preferences of surfactant protein D. Am J Respir Cell Mol Biol. 35, 84-94.

Head, J.F., Mealy, T.R., McCormack, F.X., and Seaton, B.A. (2003) Crystal Structure of Trimeric Carbohydrate Recognition and Neck Domains of Surfactant Protein A. J. Biol. Chem. 278, 43254-60.

Contact Us

Department of Pharmacology, Physiology & Biophysics
Chobanian & Avedisian School of Medicine
700 Albany Street
Boston MA 02118-2526

Phone:(617) 358-8445
e-mail: seatonba@bu.edu