SPP 1132: Proteolysis in Prokaryotes: Protein Quality Control and Regulatory Principle
Biology
Final Report Abstract
Around the year 2000 it had become clear that also in bacteria proteolytic processes are crucially important for (i) cellular protein quality control, i.e. the removal of denatured and aggregated proteins, and (ii) the regulation of complex and important cellular processes such as bacterial stress responses, cell cycle, development and virulence. The molecular details and physiological implications, however, were largely unknown. As a consequence the DFG Priority Programme 1132 “Proteolysis in Prokaryotes: Protein Quality Control and Reguatory Principles“ was established and lasted from 2002 to 2008. Research done within the SPP 1132 framework has dramatically contributed to the rapid progress in this scientific field. Members of SPP 1132 have played an internationally leading role in elucidating processes of proteolytic substrate recognition in prokaryotes and regulatory networks that are essentially affected by proteolysis of key regulators. They have significantly contributed to the determination of the molecular structures of bacterial chaperone/protease complexes, they have played a pivotal role in the emergence of the concept that proteolytic events occur at distinct cellular locations despite the small size of the bacterial cell, and even demonstrated that proteolytic processes can serve as targets for new antibiotics. SPP 1132 has in fact generated an internationally highly visible German research community in the field of prokaryotic proteolysis by (i) establishing intensive longterm collaborations among a number of groups involved, and (ii) organizing intensely interactive scientific meetings on an annual basis. The latter included three international symposia (in 2002, 2005, and 2008) of a small Gordon Conference-like formate that were internationally announced, gathered between 85 and 120 participants, represented the very first international meetings with a focus on prokaryotic proteolysis, and in fact turned out to organize even the international community in this field. A strong international element was introduced into SPP 1132 also by the fact that several of its project leaders were located abroad for part of the priority programme´s life-time and during this time had the status of ‘associated member‘. Of the 16 project leaders associated with SPP 1132, nine experienced professional promotions during the life-time of the priority programme, including six who received offers of full professorships. Within SPP 1132 a total of 26 doctoral theses and more than 130 scientific publications (many in top journals) were generated. In conclusion, SPP 1132 has fostered a stable, communicative and scientifically extremely successful national research community in the field of prokaryotic proteolysis that will clearly continue to be productive and internationally competitive in the future.
Publications
- Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine.
Nature, Vol. 416. 2002, pp. 455–459.
Krojer T., Garrido-Franco M., Huber R., Ehrmann M., Clausen T.
(See online at https://doi.org/10.1038/416455a) - Protein folding and degradation in bacteria: to degrade or not to degrade? That is the question. Cellular and Molecular Life Sciences CMLS, Vol. 59. 2002, pp. 1607–1616.
Dougan, D.A., Mogk, A., Bukau, B.
(See online at https://doi.org/10.1007/PL00012487) - MecA, an adaptor protein necessary for ClpC chaperone activity. Proceedings of the National Academy of Sciences of the USA, Vol. 100. 2003, Issue 5, pp. 2306-2311.
Schlothauer, T., Mogk, A., Dougan, D.A., Bukau, B. & Turgay, K.
(See online at https://doi.org/10.1073/pnas.0535717100) - The absence of FtsH metalloprotease activity causes overexpression of the sigmaW-controlled pbpE gene, resulting in filamentous growth of Bacillus subtilis. Journal of Bacteriology, Vol. 185.2003, Issue 3, pp. 973-982.
Zellmeier, S., Zuber, U., Schumann, W., Wiegert, T.
(See online at https://doi.org/10.1128/JB.185.3.973-982.2003) - Peptidoglycan amidase MepA is a LAS metallopeptidase. Journal of Biological Chemistry, Vol. 279.2004, Issue 42, pp. 43982-43989.
Marcyjaniak, M., Odintsov, S.G., Sabala, I., Bochtler, M.
(See online at https://dx.doi.org/10.1074/jbc.M406735200) - The Thermoplasma acidophilum Lon protease has a Ser-Lys dyad active site.
European Journal of Biochemistry, Vol. 271. 2004, Issue 22, pp. 4361-4365.
Besche H., Zwickl P.
(See online at https://doi.org/10.1111/j.1432-1033.2004.04421.x) - A two-component phosphotransfer network involving ArcB, ArcA and RssB coordinates synthesis and proteolysis of σS in Escherichia coli. Genes & Development, Vol. 19. 2005, Issue 22, pp. 2770-2781.
Mika, F., Hengge, R.
(See online at https://dx.doi.org/10.1101/gad.353705) - The transcriptional activator ClgR controls transcription of genes involved in proteolysis and DNA repair in Corynebacterium glutamicum. Molecular Microbiology, Vol. 57. 2005, Issue 2, pp. 576-591.
Engels, S., Ludwig, C., Schweitzer, J.E., Mack, C., Bott, M., Schaffer, S.
(See online at https://doi.org/10.1111/j.1365-2958.2005.04710.x) - Alanine dehydrogenase activity is required for adequate progression of phycobilisome degradation during nitrogen starvation in Synechococcus elongatus PCC 7942. Journal of Bacteriology, Vol 188. 2006, Issue 14, pp. 5258-5265.
Lahmi, R., Sendersky, E., Perelman, A., Hagemann, M., Forchhammer, K., Schwarz, R.
(See online at https://doi.org/10.1128/JB.00209-06) - The C-terminal end of LpxC is required for degradation by the FtsH protease.
Molecular Microbiology, Vol. 59. 2006, Issue 3, pp. 1025-1036.
Führer, F., Langklotz, S. F. Narberhaus
- The structure of RseB: a sensor in periplasmic stress response of E. coli. Journal of Molecular Biology, Vol. 372. 2007, Issue 4, pp. 927-941.
Wollmann P, Zeth K.
(See online at https://doi.org/10.1016/j.jmb.2007.06.039) - The tyrosine kinase McsB is a regulated adaptor protein for ClpCP.
EMBO Journal, Vol. 26. 2007, Issue 8, pp. 2061-2070.
Kirstein, J., Dougan, D.A., Gerth, U., Hecker, M. & Turgay, K.
(See online at https://doi.org/10.1038/sj.emboj.7601655) - Interplay of PDZ and protease domain of DegP ensures efficient elimination of misfolded proteins. Proceedings of the National Academy of Sciences of the USA, Vol. 105. 2008, Issue 22, pp. 7702-7707.
Krojer T., Pangerl K., Kurt J., Sawa J., Stingl C., Mechtler K., Huber R., Ehrmann M., Clausen T.
(See online at https://doi.org/10.1073/pnas.0803392105) - Mitofusin 2 Builds a Bridge between ER and Mitochondria. Cell, Vol. 135. 2008, Issue 7, pp. 1165-1167.
Merkwirth, C. Langer, T.
(See online at https://doi.org/10.1016/j.cell.2008.12.005) - AAA proteases in mitochondria: diverse functions of membranebound
proteolytic machines. Research in Microbiology, Vol. 160. 2009, Issue 9, pp. 711-717.
Tatsuta T, Langer T.
(See online at https://doi.org/10.1016/j.resmic.2009.09.005) - Deg/HtrA proteases as components of a network for photosystem II quality control in chloroplasts and cyanobacteria. Research in Microbiology, Vol. 160. 2009, Issue 9, pp. 726-732.
Huesgen, P. F., Schuhmann, H. Adamska, I.
(See online at https://doi.org/10.1016/j.resmic.2009.08.005) - The general stress response in Gram-negative bacteria. In: Bacterial Stress
Responses, eds. G. Storz and R. Hengge. ASM Press, 2010, pp. 251-289.
Hengge, R.
(See online at https://doi.org/10.1128/9781555816841.ch15)
