Electric Ant Lab (Netherlands)

Dynamin belongs to the large GTPase superfamily, and mediates the fission of vesicles during endocytosis. Dynamin molecules are recruited to the neck of budding vesicles to assemble into a helical collar and to constrict the underlying membrane. Two helical forms were observed: the one-start helix in the constricted state and the two-start helix in the super-constricted state. Here we report the cryoEM structure of a super-constricted two-start dynamin 1 filament at 3.74 Å resolution. The two strands are joined by the conserved GTPase dimeric interface. In comparison with the one-start structure, a rotation around Hinge 1 is observed, essential for communicating the chemical power of the GTPase domain and the mechanical force of the Stalk and PH domain onto the underlying membrane. The Stalk interfaces are well conserved and serve as fulcrums for adapting to changing curvatures. Relative to one-start, small rotations per interface accumulate to bring a drastic change in the helical pitch. Elasticity theory rationalizes the diversity of dynamin helical symmetries and suggests corresponding functional significance.

Understandinghow emerging influenza viruses recognize host cellsis critical in evaluating their zoonotic potential, pathogenicity,and transmissibility between humans. The surface of the influenzavirus is covered with hemagglutinin (HA) proteins that can form multipleinteractions with sialic acid-terminated glycans on the host cellsurface. This multivalent binding affects the selectivity of the virusin ways that cannot be predicted from the individual receptor–ligandinteractions alone. Here, we show that the intrinsic structural andenergetic differences between the interactions of avian- or human-typereceptors with influenza HA translate from individual site affinityand orientation through receptor length and density on the surfaceinto virus avidity and specificity. We introduce a method to measurevirus avidity using receptor density gradients. We found that influenzaviruses attached stably to a surface at receptor densities that correspondto a minimum number of approximately 8 HA–glycan interactions,but more interactions were required if the receptors were short andhuman-type. Thus, the avidity and specificity of influenza virusesfor a host cell depend not on the sialic acid linkage alone but ona combination of linkage and the length and density of receptors onthe cell surface. Our findings suggest that threshold receptor densitiesplay a key role in virus tropism, which is a predicting factor forboth their virulence and zoonotic potential.