Design of coiled coils for novel biotechnology applications

Coiled coils are essential subunit oligomerization motifs in proteins and are found in almost one-third of all proteins [1]. The Stetefeld lab carried out foundational work, including (i) the exploration of the very first S-layer protein X-ray crystal structure from the archea Staphylothermus marinus [2] as well as (ii) the unique storage properties of human cartilage oligomerization matrix protein for lipophilic compounds such as vitamin D3 and several fatty acids [3,4]. This is an exciting new frontier combining oligomerization power with the unique and highly selective storage and delivery properties of coiled coils.

For example, we showed that these motifs could be used as “carrier-pathfinder systems” for targeted drug delivery [5]. Importantly, our discoveries enabled the foundation of COGRAD in 2014. Based on rigorous structure-property studies, the unique features of coiled-coil nanotubes for the uptake of polycyclic aromatic hydrocarbons are exploited to develop unique monitoring and remediation devices for the oil and gas industry.

Our work presents the first application of an integrated structural biology approach for the exploration of extracellular S-layer components guiding the design and application of biodegradable devices for industry applications. Recently we could demonstrate that our nanotubes are able to uptake elemental sulfur S8 crowns [6], reduce ionic metal compounds to store them as metallic clusters inside the cavities [7] and can be applied as highly-efficient monitoring devices for PACs [8].

[1] Burkhard et al. TICB, 2001 [2] Stetefeld et al. Nature Structural Biology, 2001 [3] Oezbek et al. EMBO J, 2002 [4] McFarlane et al. PLoS One, 2012 [5] McFarlane et al. Eur J Pharmacol 2009 [6] McDougall et al. Proteins, 2018 [7] McDougall et al. JSB, 2018 [8] McDougall et al. Scientifc Reports, 2019