bi400677n_si_001.pdf (7.78 MB)
Human (α2→6) and Avian (α2→3) Sialylated Receptors of Influenza A Virus Show Distinct Conformations and Dynamics in Solution
journal contribution
posted on 2013-10-15, 00:00 authored by Guilherme
L. Sassaki, Stefano Elli, Timothy
R. Rudd, Eleonora Macchi, Edwin A. Yates, Annamaria Naggi, Zachary Shriver, Rahul Raman, R. Sasisekharan, Giangiacomo Torri, Marco GuerriniDifferential
interactions between influenza A virus protein hemagglutinin
(HA) and α2→3 (avian) or α2→6 (human) sialylated
glycan receptors play an important role in governing host specificity
and adaptation of the virus. Previous analysis of HA–glycan
interactions with trisaccharides showed that, in addition to the terminal
sialic acid linkage, the conformation and topology of the glycans,
while they are bound to HA, are key factors in regulating these interactions.
Here, the solution conformation and dynamics of two representative
avian and human glycan pentasaccharide receptors [LSTa, Neu5Ac-α(2→3)-Gal-β(1→3)-GlcNAc-β(1→3)-Gal-β(1→4)-Glc;
LSTc, (Neu5Ac-α(2→6)-Gal-β(1→4)-GlcNAc-β(1→3)-Gal-β(1→4)-Glc]
have been explored using nuclear magnetic resonance and molecular
dynamics simulation. Analyses demonstrate that, in solution, human
and avian receptors sample distinct conformations, topologies, and
dynamics. These unique features of avian and human receptors in solution
could represent distinct molecular characteristics for recognition
by HA, thereby providing the HA–glycan interaction specificity
in influenza.