Abstract
Single Particle Cryo-EM of Helicobacter pylori Trimeric Urease
Urease, urea amidohydrolase, can be found in many organisms other than mammals. Most of the discovered ureases are nickel enzymes. It facilitates Helicobacter pylori colonization in stomach, likely through the production of acid-neutralizing ammonia. Urease maturation requires four accessory proteins, UreE, UreF, UreG and UreH. Metallochaperone UreE passes the nickel to UreG via the formation of UreE2G2 complex in the presence of GTP. Nickel-bound UreG dimer is thought to switch to the pre-formed complex UreF2H2/Urease. Upon GTP hydrolysis of UreG, the nickel may translocate to urease via a water tunnel in the UreF2H2 complex.
Native plant ureases have a hexameric structure, while most of the bacterial ureases are trimeric. Helicobacter pylori urease has a very special dodecameric structure. Despite the different quaternary structures, the ureases have high sequence homology and similar folding. Interestingly, a large population of H. pylori urease trimer co-exists with the dodecamer during protein purification. However, unlike other bacterial ureases, H. pylori urease trimer could not be activated. Pulldown assay indicated a differential binding with HisGST-UreF/UreH complex between H. pylori urease dodecamer and trimer. Without any sign of protein degradation, we hypothesize that there may be structural differences between urease trimer and dodecamer. The difference may affect both the tetramerization of the urease trimer and its interaction with UreH. Single particle cryo EM is employed to determine the structure of H. pylori trimeric urease.
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