Structural Basis and Evolution of Glycan Receptor Specificities within the Polyomavirus Family.

Asymptomatic infections with polyomaviruses in humans are common, but these small viruses can cause severe diseases in immunocompromised hosts. New Jersey polyomavirus (NJPyV) was identified via a muscle biopsy in an organ transplant recipient with systemic vasculitis, myositis, and retinal blindness, and human polyomavirus 12 (HPyV12) was detected in human liver tissue. The evolutionary origins and potential diseases are not well understood for either virus.

The Symmetry of Viral Sialic Acid Binding Sites-Implications for Antiviral Strategies.

Virus infections are initiated by the attachment of the viral particle to protein or carbohydrate receptors on the host cell. Sialic acid-bearing glycan structures are prominently displayed at the cell surface, and, consequently, these structures can function as receptors for a large number of diverse viruses. Structural biology research has helped to establish the molecular bases for many virus-sialic acid interactions.

Structural and biochemical analysis of a phosin from Streptomyces chartreusis reveals a combined polyphosphate- and metal-binding fold.

X-ray crystallographic analysis of a phosin (PptA) from Steptomyces chartreusis reveals a metal-associated, lozenge-shaped fold featuring a 5-10 Å wide, positively charged tunnel that traverses the protein core. Two distinct metal-binding sites were identified in which the predominant metal ion was Cu . In solution, PptA forms stable homodimers that bind with nanomolar affinity to polyphosphate, a stress-related biopolymer acting as a phosphate and energy reserve in conditions of nutrient depletion.

Divalent Sialylated Precision Glycooligomers Binding to Polyomaviruses and the Effect of Different Linkers.

Divalent precision glycooligomers terminating in N-acetylneuraminic acid (Neu5Ac) or 3'-sialyllactose (3'-SL) with varying linkers between scaffold and the glycan portions are synthesized via solid phase synthesis for co-crystallization studies with the sialic acid-binding major capsid protein VP1 of human Trichodysplasia spinulosa-associated Polyomavirus. High-resolution crystal structures of complexes demonstrate that the compounds bind to VP1 depending on the favorable combination of carbohydrate ligand and linker. It is found that artificial linkers can replace portions of natural carbohydrate linkers as long as they meet certain requirements such as size or flexibility to optimize contact area between ligand and receptor binding sites.