Biology Reference
In-Depth Information
domain called SH2 allowing phosphotyrosine binding is present
115 times in the human genome, while the sequence of domain SH3
of the tyrosine kinase CsK is present 253 times (Pawson and Nash,
2003). In addition, these repeated domains often recognise very
short binding sequences which are only four to ten amino acids long.
For this reason these sequences are themselves present in a large
number of proteins, which are just as many potential molecular
partners. The domain SH3 thus recognises the amino acid sequence
P-X-X-P.
22
Countless other interaction domains favourable to such
combinations have been identified (Castagnoli
et al
., 2004).
4.2.2
The plasticity of interaction sites
Another reason for molecular non-specificity puts paid to the idea
we have of there being one molecular interaction between two well-
defined entities. Not only are the same interaction domains present
in many proteins, but a single protein domain can bind to different
ligands. The domain of SMAD proteins called MH2 provides an
example. These proteins are used in transducing signals between
the cell membrane and the nucleus, where they modulate the activ-
ity of several genes. During this transfer their MH2 domain inter-
acts with many partners carrying different binding sequences
(Pawson and Nash, 2003). This phenomenon causes the number of
combinations of possible interactions to be multiplied and challenges
the static view of stereospecificity. Indeed, for a single domain the
possible ligands can be very different, in form, size and amino acid
composition. The number of arguments indicating that this phe-
nomenon is due to a protein interaction site not being a static entity,
but a dynamic one, is growing. Its three-dimensional structure is
not rigid but flexible. It constantly changes its configuration. A pro-
tein in solution would in reality be a population composed of a mix-
ture of several conformations in dynamic equilibrium, each with a
particular potential 'specificity'. Structures deduced by crystalli-
sation are in fact only frozen images which eliminate this diversity
22
P
=
proline and X
=
any amino acid.
