Membrane Proteins

Membrane proteins constitute over 25% of predicted proteins, and represent the majority of today’s drug targets in pharmaceutical research. Membrane proteins are of central importance for health and disease. Nevertheless, only ~300 structures of membrane proteins have been determined, compared to more than 37,000 available structures of soluble proteins.

One of the possible applications of cryo-EM is the study of membrane protein structures. While the high-resolution structure of many membrane proteins can efficiently be determined by XRD or NMR, the structure and arrangement of larger membrane protein complexes or the dynamic conformation of certain membrane protein systems in the biological membrane are best studied by analyzing them in the lipid membrane environment.

With Crina Nimigean, Cornell University, NY, we have characterized cyclic-nucleotide gated potassium channels by single particle EM and electron crystallography and obtained a first direct characterization of the orientation of the voltage sensor “paddles” in the membrane embedded conformation (Chiu et al., Structure 2007). In collaboration with Joe Mindell, NIH, Washington, we study the E. coli chloride/proton antiporter.

Membrane Protein Complexes

We also studies protein complexes, partly in collaboration with other laboratories. With Guy Cornelis, Biozentrum Basel, we study the structure of the type-III secretion system complex. We are approaching this complex with cryo-EM investigations of individual subunit complexes, as well as cryo-electron tomography and sub-volume averaging of the entire bacterial complex.

Workshop on Electron Crystallography

Together with Ben Hankamer, University of Queensland, Austroalia, and Tom Walz, Harvard Med. School and HHMI, Boston, MA, USA, we organize a biennial Workshop on Electron Crystallography of Membrane Proteins. The one-week workshop is aimed at PhD students, PostDocs, and beyond, who are interested in the structure determination of membrane proteins (or other 2D protein crystal arrays) by electron crystallography. The workshops feature lectures in the morning, practicals in the afternoon, student poster session before dinner, and science talks in the evening. Practicals concern membrane protein crystallization by different methods, sample preparation for cryo-EM, data collection by cryo-EM imaging and electron diffraction, and computer image processing. The workshop features ~20 lecturers and is limited to ~20 students. A first workshop took place at UC Davis in Aug. 6-11, 2006. The second workshop took place at UC Davis in Sept. 7-13, 2008. The third workshop in this series is took place in Aug. 1-7, 2010, in Basel, Switzerland.