Biology Reference
In-Depth Information
produced by binding RNA so, once the complete length of TMV RNA has been packaged,
further growth ceases. The RNA therefore acts as a 'molecular ruler' that determines the
precise length of the finished virus.
The ability of an entire virus to organize itself
in vitro
from a simple mixture of its compon-
ents is a remarkable illustration of the power of self-assembly for small structures. Indeed,
the first demonstration of TMV self-assembly, by Fraenkel-Conrat and Williams in 1955,
caused a sensation in the popular press at the time, being heralded as the creation of 'life
in a test tube'. Most biologists would, however, distance themselves from the idea that assem-
bling a virus from its constituent components is creation of 'life', for the virus can only propa-
gate with the help of a vast number of systems in a host cell, and the host cell certainly cannot
be created by mixing its components
in vitro
.
QUAL
ITY CONTROL IN SELF-ASSEMBLING STRUCT
URES
Although they are simple, self-assembling structures are nevertheless able to perform
limited error correction and quality control. Their ability to do this comes from two main
sources: the relative strengths of their chemical bonds, and the use of binding sites to which
more than one monomer contributes.
The relatively weak bonds that connect the molecules of biological self-assembling struc-
tures are based on hydrogen bonding and dipolar and van der Waals interactions. These are
orders of magnitude weaker than the covalent linkages used within the constituent mol-
ecules themselves; for example, compare the mean bond dissociation enthalpy of a C
d
C
covalent bond (348 kJ/mol) with that of a hydrogen bond (10
d
30 kJ/mol).
24,25
All chemical
bonds are equilibria but, for most covalent bonds within biological molecules, the equilib-
rium is located so far towards the bonded state that the fact of the equilibrium can almost
be disregarded and the covalent bonds can be regarded as essentially permanent. There
are of course exceptions, particularly for the small molecules of intermediary metabolism
and for regulatory groups such as phosphates, but the foregoing is true for most bonds
within
most structural molecules. The weakness of
inter
molecular bonding, however, means that the
fact of the equilibrium between molecules in the bound and unbound states is significant and
even if the average direction of progress is towards polymerization, the addition of any
particular subunit is reversible. In the case of misfit subunits, for which the bonding energy
is even lower (because of the misfit), it is especially likely that the subunit will dissociate
again and that the error will therefore be corrected.
26
The second source of error correction, common in self-assembling structures but by no
means universal, is the use of binding sites for a new component that are created or exposed
only when earlier components in the sequence of assembly are bound correctly. For example,
bacteriophages such as T4 assemble their many different types of component in a strict order,
and the binding site for a late-adding component is usually created by the binding of its
predecessor.
27,28
The use of this strategy has two consequences: (1) It forces the associations
between components to take place in a specific order; and (2) it prevents further construction
of an assembly that has just incorporated a misaligned or wrong component until that erro-
neous component has dissociated (in the thermodynamic equilibrium described above) and
been replaced with a correct one.
