Inside story: Structural studies of membrane proteins
Membrane proteins make up around 25 per cent of all proteins (and 40 per cent of drug targets). Yet, because membrane proteins are so hard to work with, relatively few structural studies have been carried out on them. A dedicated Membrane Protein Laboratory, led by Imperial College London's So Iwata, has been set up with Wellcome Trust funding at the Diamond synchrotron, to act as a resource to support structural studies of membrane proteins. Work on a bacterial transporter illustrates the kind of insights that structural studies can provide.
Mhp1, a membrane protein from Microbacterium liquifaciens, has a 'metabolic salvage' function. It imports derivatives of the organic molecule hydantoin, which are used to make a variety of amino acids. It is an important 'model' structure as it is one of a large class of similar transporters: more than 800 are known in total, from all classes of life. Its structure was worked out at the Membrane Protein Laboratory by Professor Iwata in collaboration with Peter Henderson from the University of Leeds and others (ref. 1).
Of greatest interest, the structure suggests a mechanism for the specific transport of its substrate - confirming the 'alternating access' model proposed many years ago for the action of membrane transporters.
Without substrate, a central chamber is exposed to the outside environment. When hydantoin engages, it triggers a conformational change that in effect closes the door to the entry of further molecules. A second shift in structure exposes hydantoin to the inside of the cell, where it is ejected and the transporter reverts to its original structure.
The structure is likely to have relevance beyond the world of bacteria. Many membrane transporters, in all kinds of organisms, are thought to operate through the alternating access mechanism. This work should therefore aid understanding of other structures that move molecules across membranes.
This research was supported by the Wellcome Trust and other funders.
Image: Structure of the Mhp1 membrane protein. Credit: Membrane Protein Laboratory
References
1 Weyand S et al. Science 2008;322(5902):709-13.