Structural basis for protocadherin-1 recognition by New World hantaviruses.

A Nature study resolved the near-atomic-resolution structure of the Andes virus spike protein in complex with the PCDH1 receptor. PCDH1 binds asymmetrically in a deep pocket formed by four Gn protomers, explaining why only intact virions or soluble tetramers recognize the receptor. Mutagenesis identified three Gn loops shaping the binding site and enabled transfer of receptor binding from New World to Old World glycoproteins. Four neutralizing antibodies block receptor binding through two mechanisms: masking the binding site or steric hindrance, providing a structural framework for anti-hantavirus drug design.