Unravelling Helicobacter: Bactofilin insights from NMR

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  • Published: Dec 15, 2015
  • Author: David Bradley
  • Channels: NMR Knowledge Base
thumbnail image: Unravelling Helicobacter: Bactofilin insights from NMR

Novel NMR

A novel approach to solid-state NMR spectroscopy has allowed researchers to unravel stryuctureal details of bactofilin from the ulcer-causing corkscrew bacterium, Helicobacter pylori.

A novel approach to solid-state NMR spectroscopy has allowed researchers to unravel structural details of bactofilin from the ulcer-causing corkscrew bacterium, Helicobacter pylori.

The conventional wisdom has it that bacteria are simple, primitive, organisms. Indeed, it was thought that bacteria do not have a stabilising cytoskeleton, but today scientists are increasingly aware of the presence of complex architectures that are similar to the larger and in evolutionary terms more modern cells of plants and animals. The true complexity of bacteria is only just now being revealed through modern imaging and other techniques.

Skeleton structure

Now, Berlin biophysicist Adam Lange of the Leibniz-Institut für Molekulare Pharmakologie (FMP), Germany, is getting closer and closer to the fine structural details and has succeeded in zooming in on the basic building blocks of the bacterial skeleton of H. pylori, a microbe infamous and Nobel winning that burrows into the lining of the stomach and leads to the development of painful and often debilitating ulcers. This building block, the cytoskeletal protein bactofilin could represent a novel target for the development of new antibiotics against this bacterium and others that use related compounds.

Bactofilin itself was discovery just five years ago and gives H. pylori its typical corkscrew-shaped form, which allows it to bore into the protective mucous layer of the inner wall of the stomach. The individual bactofilin molecules polymerise spontaneously in the interior of the bacteria to form thin fibres and higher order structures. Earlier in the year, Lange and colleagues published details of an unusual structural motif present in bactofilin. They revealed a beta-helical fold that had never before been found in a cytoskeleton. Of course, such fibre proteins are resistant to crystallization and thus diffraction studies as well as being insoluble and so no amenable to solution spectroscopy. As such, team members Chaowei Shi and Pascal Fricke turned to solid-state NMR spectroscopy and extended the technique at FMP to allow them to obtain particularly high resolution spectra. They focused on four-dimensional (4D) HN-HN and 2D C-C NMR spectroscopy of labelled samples.

Core domain

On the basis of unambiguous restraints from these spectra, the team demonstrated that the core domain of bactofilin forms a right-handed beta helix with six windings and a triangular hydrophobic core. The precise form of the bactofilin building blocks and their chemical properties are now known, so it should be possible to search for small molecules that interfere with the polymerisation of the fibres and might lead to drug candidates.

"All processes in living organisms are ultimately driven by proteins, and we have to know their structures in order to understand how they function," explains Lange. "Impressive breakthroughs have also been achieved in the field of cryo-electron microscopy over the past few years, and we want to establish co-operations here," he adds. "If one wants to understand protein structures in all their dimensions and details, experts must not work on their own in isolation, but rather we must integrate the modern powerful techniques into joint projects."

Related Links

Sci Adv 2015, 1, e1501087: "Atomic-resolution structure of cytoskeletal bactofilin by solid-state NMR"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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