Molecular Mechanism of SLC26 Transport

SLC26 proteins are composed of a membrane-embedded transport domain and a cytoplasmic STAS domain. Thus far three high-resolution structures of SLC26 proteins are available. These structures provided valuable first insights into the molecular architecture of the protomer and the dimer. Here we aim at a broader and general understanding of SLC26 molecular structure and dynamics to detail the transport mechanisms.

In addition to structure determination, we use extensive molecular dynamics simulations and experimental structure-function approaches to thoroughly define the mechanisms of anion binding and transport. Importantly, close and iterative interaction between structural and computational biologists as well as molecular physiologists will ensure that experimentally determined structures and functional data will instruct each other, while both will be interpreted by in silico simulations to unravel underlying dynamic processes, together leading to a deep mechanistic understanding of transport function. Finally, atomic-level insights into functional dynamics will provide a solid basis for pharmacological target identification and structure-based virtual screening of future drug candidates.

Principal Investigators

Dr. Eric Geertsma
Prof. Dr. Jan-Philipp Machtens
Prof. Dr. Dominik Oliver
Prof. Dr. Christoph Fahlke