An Arginine Switch in the Species B Adenovirus Knob Determines High-Affinity Engagement of Cellular Receptor CD46

• DOI: 10.1128/jvi.01967-08
• Publication Date: 2008-11-06T01:46:47Z
• Authors: B. David Persson; Steffen Müller; Dirk M. Reiter; Benedikt B. T. Sc...; Marko Marttila; Chris Vanessa Sum...; Sabine Schweizer; Ulrike Scheu; Christian Ochsenfeld; Niklas Arnberg; Thilo Stehle
• Keywords: HEK 293 cells

Adenoviruses (Ads) are icosahedral, nonenveloped viruses with a double-stranded DNA genome. The 51 known Ad serotypes exhibit profound variations in cell tropism and disease types. number of observed infections is steadily increasing, sometimes leading to fatal outcomes even healthy individuals. Species B Ads can cause kidney infections, hemorrhagic cystitis, severe respiratory most them use the membrane cofactor protein CD46 as cellular receptor. crystal structure human type 11 (Ad11) knob complexed known; however, determinants binding related species remain unclear. We report here structural functional analysis Ad11 knob, well Ad7 Ad14 knobs, which closely sequence but have altered CD46-binding properties. comparison structures three we determined at very high resolution, provides platform for understanding these differences allows us propose mechanism productive high-affinity engagement CD46. At center this an arginine that needs switch its orientation order engage affinity. Quantum chemical calculations showed affinity significantly higher than Ad7. Thus, while also bind CD46, kinetics interactions suggest unlikely productively. proposed likely determine receptor usage all Ads.