Cryo electron microscopy of membrane proteins and biomolecular assemblies - Hans Hebert
Mucins are large glycoproteins that coat the surface of cells in the respiratory, digestive, and urogenital tracts. The first insights into the packing and secretion of intestinal MUC2 in molecular terms have now been obtained. Purified MUC2-N protein was analyzed by electron microscopy and image processing, suggesting how MUC2-N is packed in granulae of goblet cells. Dysregulation of the normal >1000-fold expansion upon release could explain the extreme viscosity of the produced mucus seen in cystic fibrosis.
A refined atomic model of microsomal glutathione transferase 1 in a lipid bilayer environment has been determined using electron crystallography. It is shown that glutathione binds in a different conformation as compared to other proteins from the same superfamily. Information unique to the methodological approach shows interactions between lipids and protein. Furthermore, we have determined conformational changes occurring as a result of second substrate binding giving further insight into the catalytic mechanism. Key residues determining species differences in inhibitor binding of microsomal prostaglandin E synthase-1 have been identified.
Structural studies of a putative potassium channel suggest a new arrangement the soluble domains regulating the conductance of K+-ions in these types of channels.
The properties of polymer microbubbles, intended to be used for multimodal medical imaging, have been studied by electron microscopy both with regard to ultrastructure and distribution in different organs.
The membrane-bound detoxification enzyme microsomal glutathione transferase 1. The electron diffraction pattern was recorded from a two-dimensional crystal of the protein. The inset shows the corresponding 3D map at 3.5 Å resolution as reconstructed from a large number of such patterns obtained from a distribution of projection directions. The viewing direction is perpendicular to the plane of the membrane. Each triangular structure corresponds to one trimer of the protein having twelve transmembrane alpha helices.