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VINZENZ UNGER

General Overview
Cells could not exist without membranes and their resident proteins. Besides being involved in fundamental processes such as solute transport and signaling across the membrane, membrane proteins also make for ~70% of current drug targets. Yet, progress in gaining detailed mechanistic understanding of membrane protein function is hampered by a lack of structural information because structural biology of membrane proteins and their supramolecular assemblies remains a challenging and mostly uncharted terrain. We use a combination of structural, biochemical and biophysical approaches to understand general design principles of membrane proteins, and how these proteins interact with each other as well as with upstream/downstream partners to form macromolecular assemblies that are involved in a variety of processes, ranging from translocation of transition metal ions across the membrane to synaptic signaling. Currently our work is focused on three broad subject areas:

Transport of Transition Metals
Transition metals such as iron and copper are essential for life. We are currently working on two systems that are involved in the uptake of ferrous iron in bacteria, and of copper in humans. Our primary focus is to gain insights into structure-function relationships of the membrane proteins that are involved in these processes.

Structure and Function of Membrane Associated Synaptic Scaffolds
Conceptually, synaptic signal transmission is a simple process. On closer inspection, however, synaptic signaling requires the finely tuned action of a large number of macromolecular assemblies whose exact interplay, regulation and plasticity are beyond current comprehension. Facing this "cacophony" of intermolecular interactions, our work is focused on understanding how membrane associated scaffolds engage their up- and down-stream partners, including the membrane itself, and what structural changes occur as the molecular composition of signaling complexes is altered.

Methods Development for Membrane Protein Crystallization and Single Particle Approaches
Despite tremendous progress in the structure determination of bacterial membrane proteins, determining the structure of mammalian membrane proteins still remains an art. Using electron crystallography on membrane proteins that are embedded in a lipid bilayer as well as single particle analysis of macromolecular membrane protein complexes, our efforts are focused on developing crystallization tags and scaffolds that will facilitate the structure determination of membrane proteins by electron microscopic approaches.

Selected Publications

Marlovits, T.C., Kubori, T., Sukahn, A., Thomas, D., Galán, J. and Unger, V.M. Structural insights into the assembly of the Type III secretion needle complex. Science 306, 1040-42 (2004)

Aller, S.G. and Unger, V.M.. Projection structure of the human copper transporter at 6Å reveals a compact trimer with a novel channel-like architecture. Proc. Natl. Acad. Sci. USA 103, 3627-32 (2006)

Marlovits, T.C., Kubori, T., Lara-Tejero, M., Thomas, D., Unger, V.M. and Galán J.E. Assembly of the inner rod determines needle length in the Type III secretion injectisome.  Nature 441, 637-40 (2006)

Eng, T. T., Jalilian, A. R., Spasov, K. and Unger, V. M.  Characterization of a novel prokaryotic GDP dissociation inhibitor domain from the G protein-coupled membrane protein FeoB.  J. Mol. Biol. 375, 1086-1097 (2008)

Frost, A., Perera, R., Roux, A., Destaining, O., Egelman, E., De Camilli, P. and Unger, V. M.  Structural basis of membrane invagination by F-BAR domains.  Cell 132, 807-817 (2008)

Last Updated 04-21-08