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Study of molecular chaperones encoded by f1 operon of Y. Pestis for the design of E. Coli strains secreting heterologous proteins for medical and veterinary use


Foreseen Results

This work will provide further insight into the mechanism of chaperone-mediated protein secretion in bacteria, particularly with reference to the Caf1M-like subfamily of chaperones, as follows:

- X-ray data of Caf1M protein
- theoretical model of the Caf1M-Caf1 complex
- importance of the disulphide bond and "accessory sequence" to the specificity and chaperoning function of Caf1M
- localisation of active sites/interaction sites on the periplasmic chaperone and F1 subunit
- optimisation of bacterial strains producing recombinant cytokines GM-CSF, IL-1b. IL-1ra
- information on protective properties of components of the f1 operon.

It will also provide new data on molecular chaperones as a part of an intracellular innate immune system.
Knowledge about molecular chaperones, which act as an intracellular innate immune system common to all organisms provides the basis of the present project. Molecular chaperones describe a class of conservative proteins which ensure that the folding of certain other polypeptide chains and their assembly into oligomeric structures occur correctly. Chaperones have an ability to recognise and stabilise partially folded structures. Some may recognise incorrectly assembled or misfolded proteins resulting in disaggregation and a chance to refold or to facilitate degradation. In addition to the folding processes, some chaperones play an important role in polypeptide translocation across biological membranes, both into different organelles (e.g. mitochondria, endoplasmic reticulum/golgi) and into the extracellular medium. A family of periplasmic chaperones are involved in biogenesis of virulence associated surface structures in Gram negative bacteria. These chaperones specifically recognise and bind to subunits of surface structures (pili, fimbriae, polypeptide capsule), prevent non-productive aggregation of the subunits in the periplasm and probably aid in folding of the subunit, following translocation of the subunits across the inner membrane. The molecular chaperone then delivers the subunit to an outer membrane molecular usher protein which is responsible for translocation of the subunit through the outer membrane and correct assembly and anchorage of surface structures. A primary objective of this study is to explore the mechanism of function of one characteristic representative of a subfamily of these chaperones - the Caf1M protein of the f1 operon of Yersinia pestis.


University of Reading
RG6 2AJ Reading
United Kingdom

Participants (6)

Crimean Medical Institute
5-7,Lenin Bul.
Joint Stock Company Institute of Engineering Immunology

142380 Lyubuchany
Kazakh Scientific Research Anti-Plaque Institute
480074 Almaty
United Kingdom
Porton Down
SP4 0JG Salisbury
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry - Russian Academy of Sciences
16-10,Miklukho-maklaya Street
117871 Moskva
University of Turku
20520 Turku