Polysaccharide Recognition by Surfactant Protein D: Novel Interactions of a C-Type Lectin with Non terminal Glucosyl Residues
Alain Laederach BCB/Dept. of Chemical Engineering
Major Professor: Peter Reilly
Friday Feb. 16
1:10 pm
Room 1420 Molecular Biology Building
Abstract Surfactant protein D (SP-D), a C-type lectin, is an important pulmonary host defense molecule. Carbohydrate binding is critical to its host defense properties, but the precise polysaccharide structures recognized by the protein are unknown. SP-D binding to Aspergillus fumigatus is strongly inhibited by a soluble beta-(1->6)-linked (pustulan) but not by a soluble beta-(1->3)-linked (laminarin) glucosyl homopolysacchride, suggesting that SP-D recognizes only certain polysaccharide configurations, likely through differential binding to non terminal glucosyl residues. In this study we have computationally docked alpha/beta-D-glucopyranose and alpa/beta-(1->2)-, alpha/beta-(1->3)-, alpha/beta-(1->4)-, and alpha/beta-(1->6)-linked glucosyl trisaccharides into the SP-D carbohydrate recognition domain. As with a mannose-binding protein, we found significant hydrogen bonding between the protein and the vicinal, equatorial OH groups at the 3 and 4 positions on the sugar ring. Our docking studies predict that alpha/beta-(1->2)-, alpha-(1->4)-, and alpha/beta-(1->6)- but not alpha/beta-(1->3)-linked glucosyl trisaccharides can be bound by their internal glucosyl residues and that binding also occurs through interactions of the protein with the 2- and 3-equatorial OH groups on the glucosyl ring. By using various soluble glucosyl homopolysacharides as inhibitors of SP-D carbohydrate binding to Aspergillus fumigatus, we confirmed the interactions predicted by our modeling studies. Given the sequence and structural similarity between SP-D and other C-type lectins, many of the predicted interactions should be applicable to this protein family.
Cizhong Jiang
BCB 690 Student Seminar
Molecular and Computational Analysis of Myb Genes
Cizhong Jiang BCB/Dept. of Zoology and Genetics
Major Professor: Tom Peterson
Friday Feb. 16
1:10 pm
Room 1420 Molecular Biology Building
Abstract The Myb family of genes exist widely in both plants and animals, encoding a group of functionally diverse transcriptional activators that is characterized by a conserved DNA-binding domain of approximately 50 amino acids with constantly spaced Trps. The functions of most plant Myb genes are unknown, but those studied to date encode transcriptional activator proteins that regulate diverse processes including development and secondary metabolism. In our research, dozens of sorghum and maize Myb genes were sequenced. Sequence analysis revealed that both their 5' regulatory region (including 5' UTR region) and their introns are quite divergent whereas their coding regions are highly conserved. The detailed sequence composition analysis and contrasting the interspecific divergence of the sorghum Myb genes as well as other species' Myb genes would shed some light on both the evolutionary history of the Myb genes and the different evolutionary pattern and constraints. The 5' regulatory region of sorghum Myb genes were also isolated and cloned into expression vector in our research. Transgenic assay and Northern hybridization were applied to investigate those 5' regulatory regions' functions. The goal is to attempt to understand the correlation between the sequence composition and the function, and identify, with the assistance of computational techniques, conserved functional elements important for gene regulation. With the daily expanding sequence data, it is a big challenge for biologists to how to take advantage of them. It is less likely with today's tools to benefit from researches on the collection of random genes. The Myb family has certain advantages that make it well suited for this purpose. Our research would provide to biologists a bridge between computational and molecular analysis of large-scale sequence in some sense.
