Beschreibung

• Sodium/Proton (Na+/H+) antiporters are transmembrane proteins that are vital for cellular homeostasis of pH, Na+, and volume. In humans, they play key roles in pathological conditions such as cancer and cardiovascular diseases. Like other membrane proteins, Na+/H+ antiporters are very hydrophobic, and it is still challenging to study their structure. No structure of eukaryotic antiporters has been determined and only a few labs have succeeded in determining the structures of prokaryotic antiporters. Furthermore, these proteins are dynamic "nano machines" that exist in several conformations. Therefore, to understand the mechanism of these proteins, in addition to the structures of the various conformations, it is essential to study their kinetics and interactions. This project will bring together several major groups working on membrane proteins. The participants use the most advanced techniques for determination of structure and dynamics in membrane proteins in silico, in vitro and in situ in the membrane. The main goal will be to reveal the 3-dimensional structures and motion of members of the Na+/H+ antiporter family and to study their molecular mechanisms. The structures determined within this project will be used to model related proteins and to infer additional conformations. The structures and models will be used to develop testable predictions, e.g., regarding the effects of mutations of key amino acids, particularly those involved in human diseases. These will be validated experimentally using functional, biochemical and biophysical assays, which will also be used as feedback for refining the models. The partners have been engaged in various collaborations on studies of the Escherichia coli Na+/H+ antiporter (EcNhaA) and related exchangers. The proposed project will tighten and broaden these collaborations, ultimately creating a highly potent, multidisciplinary, center for transporter studies. The consortium participates include both well-recognized senior scientists, such as Hartmut Michel, the German coordinator, and promising young scientists like Meytal Landau, the Israeli coordinator. It is noteworthy that Meytal Landau and Elena Olkhova are young woman scientists, and the consortium could help establish them as leaders in the field.

Projektlaufzeit

• 01.07.2015 - 31.12.2019

Verbund/Partnerorganisation

• Technion - Israel Institute of Technology