Seminar hosted by Prof Marin Van Heel
Abstract of the event:
The transport of ions, solutes and even whole proteins across biological membranes are fundamental processes in all living organisms, carried out by specialized membrane proteins. A detailed understanding of the molecular mechanisms requires precise knowledge of the three-dimensional structure of the proteins involved, usually in more than one functional state. We have recently determined the structure of a new transporter with and without bound substrate, which will be discussed in terms of its molecular mechanism.
The crystallisation of a membrane protein usually means that the protein has to removed from its native membrane. The arrangement and distribution of membrane proteins in the membrane can however be important for understanding how they work. We use electron cryo-tomography of intact membranes, whole organelles or vitreous sections to examine the arrangement of large membrane protein complexes in mitochondria and chloroplasts. We discovered that the mitochondrial ATP synthase is arranged in long rows of dimers, which are always found at the position of highest curvature of the inner membrane cristae. Yeast mutants lacking the ATP synthase subunits thought to be responsible for dimer formation do not show this striking arrangement. Unlike the wt mitochondrial complex, the chloroplast ATP synthase is entirely monomeric, and confined to membrane regions of minimal curvature. We believe this to reflect differences in membrane potential and pH gradient in the two organelles. Visualizing the photosystem-II dimer in chloroplast membranes helps us to understand the molecular basis of lateral segregation into stacked and unstacked membrane regions.
Finally, we are developing a prototype instrument for in-focus phase contrast electron microscopy that should allow us to record tomograms and single particle images with higher contrast and, hopefully, resolution.
For more information on this lecture please contact Dr Karen Polizzi