Katrina Heyrana, Boon Chong Goh, Juan Roberto Perilla, Tam-Linh N. Nguyen,
Matthew R. England, Maria C. Bewley, Klaus Schulten, and Rebecca Craven.
Contributions of charged residues in structurally dynamic capsid
surface loops to Rous sarcoma virus assembly.
Journal of Virology, 90:5700-5714, 2016.
(PMC: PMC4886791)
HEYR2016
Extensive studies of orthoretroviral capsids have shown that many regions of the CA protein play
unique roles at different points in the virus life cycle. The N-terminal domain (NTD) flexible
loop region is one such example: exposed on the outer capsid surface, it has been implicated in
Gag-mediated particle assembly, capsid maturation and early replication events. We have now
defined the contributions of charged residues in the flexible loop (FL) region of the Rous
sarcoma virus CA to particle assembly. Effects of mutations on assembly were assessed in vivo
and in vitro and analyzed in light of new RSV Gag lattice models. Virus replication was strongly
dependent on the preservation of charge at a few critical positions in Gag-Gag interfaces. In
particular, a cluster of charges at the beginning of FL contributes to an extensive electrostatic
network that is important for robust Gag assembly and subsequent capsid maturation. Second-
site suppressor analysis suggests that one of these charged residues, D87, has distal influence on
inter-hexamer interactions involving helix 7. Overall, the tolerance of FL to most mutations is
consistent with current models of Gag lattice structures. However, the results support the
interpretation that virus evolution has achieved a charge distribution across the capsid surface
that 1) permits the packing of NTD domains in the outer layer of the Gag shell, 2) directs the
maturational rearrangements of the NTDs that yield a functional core structure, and 3) supports
capsid function during the early stages of virus infection.
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