Determining the structure and dynamics of membrane transporters

Year of award: 2015


  • Dr Argyris Politis

    King's College London

Project summary

Despite the realisation that lipids play a critical role for the structure and function of membrane proteins, the complexity of lipid-protein interactions makes them challenging to characterise by conventional tools and they remain poorly described at molecular level. Lactose permease (LacY) is a structurally well-characterised member of the major facilitator superfamily (MFS) of transporters; its dynamics however remain largely unknown.

We propose to advance knowledge regarding the conformational dynamics of LacY and its synergistic binding to lipids and other biomolecules. This will underlie efforts for drug discovery and human health.

We aim to provide an unprecedented level of molecular understanding of transmembrane transporters and their interactions with their surrounding environment. To achieve this, we will integrate a novel combination of mass spectrometry (MS)-based experiments with advanced modelling methods enabling investigation of previously intractable protein structures and molecular interactions. A key goal is to perform proof-of-principle studies on the structural dynamics of E. coli LacY and its interaction with lipids.