Carboxylate groups have been known for many years to drive the disasse
mbly of simple viruses, including tobacco mosaic virus (TMV). The iden
tities of the carboxylate groups involved and the mechanism by which t
hey initiate disassembly have not, however, been clear. Structures hav
e been determined at resolutions between 2.9 and 3.5 Angstrom for five
tobamoviruses by fiber diffraction methods. Site-directed mutagenesis
has also been used to change numerous carboxylate side chains in TMV
to the corresponding amides. Comparison of the stabilities of the vari
ous mutant viruses shows that disassembly is driven by a much more com
plex set of carboxylate interactions than had previously been postulat
ed. Despite the importance of the carboxylate interactions, they are n
ot conserved during viral evolution. Instead, it appears that during e
volution, patches of electrostatic interaction drift across viral subu
nit interfaces. The flexibility of these interactions confers a consid
erable advantage on the virus, enabling it to change its surface struc
ture rapidly and thus evade host defenses.