D. Bray et Rb. Bourret, COMPUTER-ANALYSIS OF THE BINDING REACTIONS LEADING TO A TRANSMEMBRANERECEPTOR-LINKED MULTIPROTEIN COMPLEX INVOLVED IN BACTERIAL CHEMOTAXIS, Molecular biology of the cell, 6(10), 1995, pp. 1367-1380
The chemotactic response of bacteria is mediated by complexes containi
ng two molecules each of a transmembrane receptor and the intracellula
r signaling proteins CheA and CheW. Mutants in which one or the other
of the proteins of this complex are absent, inactive, or expressed at
elevated amounts show altered chemotactic behavior and the phenotypes
are difficult to interpret for some overexpression mutants. We have ex
amined the possibility that these unexpected phenotypes might arise fr
om the binding steps that lead to active complex formation. A limited
genetic algorithm was used to search for sets of binding reactions and
associated binding constants expected to give mutant phenotypes in ac
cord with experimental data. Different sets of binding equilibria and
different assumptions about the activity of particular receptor comple
xes were tried. Computer analysis demonstrated that it is possible to
obtain sets of binding equilibria consistent with the observed phenoty
pes and provided a simple explanation for these phenotypes in terms of
the distribution of active and inactive complexes formed under variou
s conditions. Optimization methods of this kind offer a unique way to
analyze reactions taking place inside living cells based on behavioral
data.