Allosteric mechanism of trans-membrane signalling proteins

By Lizhe Zhu

Cell signalling is one of major topics in the biology community. A basic issue is the signalling process between the extra- and inner- cellular domain. For small signals, it often means that the signal can pass through some specially-structured membrane proteins, such as ions passing through ion-channels. For large signal ligands, however, direction "penetration" is less likely to happen. Allosteric mechanism is believed to the main factor: binding of signal ligands to trans-membrane receptor proteins introduces certain confirmational changes of the latter, causing subsequential inner-cellular mechanism and release of inner signals. One example is this mechanism of signal-receptor-G-protein system.

Our focus is then to model the allosteric regualtion mechanism, especially the possible cooperative mechanism of the trans-membrane signalling proteins. There has been much effort on this topic, for example, the famous MWC theory initiated in 1960's. But MWC simply assumes only two states (R & T) of each the protein subunit, unable to explain new experimental data that might imply intermediate states, so as other existing models.

We try to use coarse-graining techniques to simulate such phenomena in framework of statistical physics. We hope this statistical strategy can overcome the barrier brought by the artificially simplified assumption made in existing models. Challenging questions also include how disrete extra-celluar signals are magnified to continuous signals inside the cell. We try to update this page if essential progress is made.