The next meeting of the Structural Biology Interest Group will take place at noon on Wednesday, June 10 in the Chemistry Conference Room (HL 1135). Our speakers will be:
- Dr. Alan Zhao (PI, CVM) - "Understanding influenza A virus binding glycans: Computational identification of receptor glycan motifs and mutation effects on virus-glycan interactions." We don't normally ask for abstracts for SBIG talks, but Dr. Zhao graciously provided one, and it is included below.
- Mandi Metz (Lewis Lab, Chemistry) - "Loop Sequence Context Influences the Formation and Stability of the I-Motif for DNA Oligomers of Sequence (CCCXXX)4, where X=A and/or T, under Slightly Acidic Conditions"
Summer has officially begun, so if you have new researchers or undergraduates working in your lab, feel free to invite them if you think they may be interested. See you Wednesday!
Dr. Zhao's Abstract
Influenza A viruses (IAVs) infect various hosts through the recognition of glycans on host cells, the receptors, of which the structures have been shown to be unique in animal hosts and even within different tissues in the same host. On the receptor side, the functional substructures of glycan, so called glycan motifs, are responsible for the function or recognition of the carrier glycoconjugate and modulate these processes. Meanwhile, on the virus side, hemagglutinin (HA) is known to have high mutation frequencies that could be associated with viral host adaptations and virulence. Specific amino acid mutations on HAs of various viruses lead to significant modifications of their host receptor recognitions, which are initiated by diverse binding abilities to distinct glycans with different terminal saccharides. However, researchers almost have no clue of, first, the relationships between glycans, especially their substructure motifs, and IAVs with different host origins; second, how a given site mutation on HA affects its binding to host glycan receptors. Targeting these challenges, we developed a series of computational methodologies based on sparse learning, association mining, discrete molecular dynamics, and molecular modeling to take advantage of the information supplied by glycan microarrays and 3D structures of HA-glycan interaction complexes. On one hand, results illustrated that a few non-acidic acids (e.g. β-linked Gal and GlcNAc), and Mannose enriched terminals, in addition to the well-known α2,3- and α2,6-linked sialic acid, were identified as potential glycan motifs for IAV binding. On the other hand, our dynamic simulation strategy on a case study of HA-glycan complexes was able to calculate the converting effect of mutations that modified the HA’s receptor binding behavior. These studies shed some lights on molecular mechanisms for IAV host tropisms.