Structural Basis for how Sialoglycan-binding Viridans Streptococci Accommodate Ligands that Exceed the Characterized...

Area of Science:

• Microbiology
• Structural Biology
• Glycobiology

Background:

• Viridans group streptococci cause endocardial infections by binding to platelet glycoprotein GPIbα.
• This interaction involves streptococcal siglec-like binding regions and sialic acid-capped O-GalNAc glycans.
• Previous studies used simplified glycan fragments, limiting understanding of complex interactions.

Purpose of the Study:

• To determine the high-resolution crystal structure of a Streptococcus gordonii siglec-like binding region.
• To elucidate the binding mechanism of the L-serine-linked sialyl T antigen (sTa) trisaccharide to this protein.
• To understand how trisaccharide extensions influence sialoglycan binding.

Main Methods:

• X-ray crystallography at 1.9 Å resolution.
• Structural analysis of protein-glycan complexes.
• Biochemical assays to study binding interactions.

Main Results:

• The crystal structure of the Streptococcus gordonii M99 siglec-like binding region complexed with the sTa trisaccharide was determined.
• The structure reveals specific interactions and conformational changes accommodating the trisaccharide.
• Insights into how the protein accommodates larger, extended sialoglycan ligands were gained.

Conclusions:

• The high-resolution structure provides a detailed molecular basis for the interaction between streptococcal proteins and platelet glycans.
• Understanding this binding mechanism is crucial for developing strategies against endocardial infections.
• The findings have implications for designing inhibitors that target pathogen-host interactions.