The Howorka group is engaged in biophysically analysing biological channels to understand their function. A recent break-through has been achieved in collaboration with structural biologist Prof. Han Remaut on the CsgG channel which shuttles proteins out of the pathogenic bacteria to form curli-fibres and antibiotic-resistant biofilms, as published in Nature (1). The insight may help design strategies to interfere with biofilm formation. The analysis of the CsgG pores with single-channel electrical recordings complements current (2-4) and continues previous research interests (5,6) the engineering of and sensing with the protein nanopore α-hemolysin.
In related research, the structure of a multi-porous protein assembly was investigated to achieve a world-first. The S-layer protein lattices are major two-dimensional cell-wall component in archaea and many pathogenic and biotechnologically relevant bacteria. Initiated by our group’s examination of their molecular architecture with chemical and genetics tools (7,8), structure of an S-layer protein has been elucidated to atomic resolution (see illustration) in collaboration with Prof. Han Remaut, as published in Nature (9). This unprecedented structural insight will help guide the rational engineering of the protein lattices into vaccine carriers (10).
(1) P. Goyal, P. V. Krasteva, N. Van Gerven, F. Gubellini, I. Van den Broeck, A. Troupiotis-Tsaïlaki, W. Jonckheere, G. Péhau-Arnaudet, J. S. Pinkner, M. R. Chapman, S. J. Hultgren, S. Howorka, R. Fronzes, H. Remaut, Nature 2014, 516, 250-253.
(2) S. Buchsbaum, N. Mitchell, M. Hugh, M. Wiggin, A. Marziali, P. V. Coveney, S. Ziwy, S. Howorka, Nano Lett. 2013, 13, 3890-3896.
(3) S. Howorka, Z. S. Siwy, Nat. Biotechnol. 2012, 30, 506-507.
(4) S. Howorka, Z. Siwy, Chem. Soc. Rev. 2009, 38, 2360-2384.
(5) S. Howorka, S. Cheley, H. Bayley, Nat. Biotechnol. 2001, 19, 636-639.
(6) L. Movileanu, S. Howorka, O. Braha, H. Bayley, Nat. Biotechnol. 2000, 18, 1091-1095.
(7) H. Kinns, S. Howorka, J. Mol. Biol. 2008, 377, 589-604.
(8) H. Kinns, H. Badelt-Lichtblau, E. M. Egelseer, U. B. Sleytr, S. Howorka, J. Mol. Biol. 2010, 395, 742-753
(9) E. Baranova, R. Fronzes, A. Garcia-Pino, N. Van Gerven, D. Papapostolou, G. Péhau-Arnaudet, E. Pardon, J. Steyaert, S. Howorka, H. Remaut, Nature 2012, 487, 119-122.
(10) S. Howorka, Curr. Opin. Biotechnol. 2011, 22, 485-491.