Project Details
Projekt
Small membrane proteins as organizers of the bacterial membrane
Applicant
Professor Dr. Hans-Georg Koch
Subject Area
Metabolism, Biochemistry and Genetics of Microorganisms
Term
since 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 379070131
Small membrane proteins are defined as hydrophobic proteins of less than 50 amino acids in length, which consist primarily of a single transmembrane domain. Due to improved analytical methods, an increasing number of these proteins have been identified in eu- and prokaryotes. However, their function is in most cases unknown and they constitute the least characterized group of membrane proteins. It appears that small membrane proteins in bacteria are involved in important physiological process, like counteracting stress conditions or facilitating the assembly of membrane protein complexes. While their role as membrane chaperone or adaptor protein during the assembly of membrane protein complexes has been document in a few cases, detailed analyses on their role in the cellular stress response are missing. For obtaining a detailed view on the molecular function of small membrane proteins, the identification of their interaction partner in the membrane and on both sides of the membrane is mandatory. The interactome of selected small membrane model proteins will be determined by site-directed in vivo cross-linking in combination with mass spectrometry. This will allow to identify the cooperation of small membrane proteins with known stress response pathway and to determine how small membrane proteins influence these pathways or whether they themselves are influenced by stress response pathways.The exact localization of small membrane proteins in the bacterial cell is largely unknown and it is in particular unknown, whether these proteins form larger cluster or microdomains within the membrane. This will be analysed by electron and fluorescence microscopy, in response to internal and external stress stimuli. In addition, the impact of small membrane proteins on membrane properties, like thickness or fluidity will be determined by biophysical methods.Small membrane proteins might act as cellular protection systems against antimicrobial peptides or against toxic peptides of the toxin-antitoxin systems. This hypothesis will be validated by performing growth experiments and by analysing membrane stability. In summary, for obtaining a comprehensive insight into small membrane biology, we aim to use a multidisciplinary approach for identifying the interactome of small membrane proteins, to reveal the cellular and molecular consequences of their expression on membrane stability, architecture and stress response as well as the possibility that they are involved in neutralizing toxic peptides. For these far-reaching analyses we will employ in cooperation with the members of the SPP2002 a variety of highly relevant and sophisticated experimental strategies, which will allow an in-depth view into the physiological relevance of this so far ill-defined class of membrane proteins.
DFG Programme
Priority Programmes
