Structural basis for influence of viral glycans on ligand binding by influenza hemagglutinin.

ABSTRACT: Binding of cell surface glycans by influenza hemagglutinin controls viral attachment and infection of host cells. This binding is a three-way interaction between viral proteins, host glycans, and viral glycans; many structural details of this interaction have been difficult to resolve. Here, we use a series of 100-ns molecular dynamics simulations to further analyze available crystallographic data on hemagglutinin-ligand interactions. Based on our simulations, we predict that the viral glycans contact the host glycans within 1-2 residues of the ligand-binding site. We also predict that the glycan-glycan interactions contain both stabilizing and destabilizing components. These predictions suggest a structural means to explain why changes to viral glycosylation alter the efficiency and selectivity of ligand binding. We also predict that the proximity of these interactions to the ligand-binding pocket will impact the binding affinity of small glycomimetic ligands analogous to the influenza neuraminidase inhibitors currently in clinical use.

SUBMITTER: Kasson PM 

PROVIDER: S-EPMC2547437 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature