This tyrosine behaves in both a polar and hydrophobic manner at the same time.
4A), leaving the face of the tyrosine ring exposed to the methyl group, which may contribute hydrophobic character to the cradle. Tyr 312 would not normally be considered a hydrophobic residue, but the side-chain oxygen faces toward the solvent, where it forms a polar interaction with the C4-OH on sialic acid ( Fig. Tyr 312 may further contribute to the hydrophobic cradle. Ile 310 has the opposite orientation and creates an indentation, which cradles the methyl group of sialic acid.
However, when sialic acid is bound, it is restricted to have a single conformation with the long arm facing away from the sialic acid site, toward the intermonomer cleft. In unliganded structures of HAdV-D26K (PDB 6FJO), Ile 324 exhibits a double conformer, occupying the available space ( Fig.
The high resolution of the datasets generated to determine the sialic acid–bound HAdV-D26K structure enables visualization of multiple residue conformations with partial occupancy. We demonstrate that removal of cell surface sialic acid inhibits HAdV-D26 infection, and provide a high-resolution crystal structure of HAdV-D26 fiber-knob in complex with sialic acid. Here, we establish sialic acid as a primary entry receptor used by HAdV-D26. We recently demonstrated that HAdV-D26 does not use CD46 or Desmoglein-2 as entry receptors, while the putative interaction with coxsackie and adenovirus receptor is low affinity and unlikely to represent the primary cell receptor. HAdV-D26–derived vaccines are under investigation as protective platforms against HIV, Zika, and respiratory syncytial virus infections and are in phase 3 clinical trials for Ebola. Species D adenovirus type 26 (HAdV-D26) is both a cause of EKC and other diseases and a promising vaccine vector. As non-enveloped, double-stranded DNA viruses, they are easily manipulated, making them popular vectors for therapeutic applications, including vaccines. They cause respiratory distress, gastroenteritis, and epidemic keratoconjunctivitis. Adenoviruses are clinically important agents.
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