Cell division is one of the most fundamental and challenging processes in the life of bacteria. The divisome is a complex composed primarily of membrane proteins that assembles at mid-cell and is necessary for bacterial cell division to occur. The structural architecture of the divisome, and the organization of its transmembrane region in particular, are still mysterious. Unraveling this organization is a crucial goal for a ful understanding of the mechanisms that are involved in bacterial division and its regulation. This goal of this proposal is a structural and functional analysis of six single-span transmembrane proteins (ZipA, FtsL, FtsB, FtsQ, FtsI and FtsN) that are central to the assembly of the divisome. The proposed approach is multi-disciplinary, with a biophysical characterization of the interactions in vitro, mutagenesis, computational modeling and X-ray crystallography to study their extra-membranous domains. Our main objectives are to determine the ability of the transmembrane region of the six divisomal proteins to interact;measure the energetics of their association;and determine their structural organization. This project addresses a critical barrier to progress in understanding bacterial cell division, namely the lack of information on the structural organization of the membrane region of the divisiome. By beginning to unravel the structural and mechanistic details of the complex, this project will establish important groundwork needed for the development of new strategies for understanding and controlling bacterial growth.

Public Health Relevance

The structural architecture of the divisome - a complex of protein that is required for bacterial cell division - remains mysterious. We propose to study six divisomal membrane proteins (ZipA, FtsL, FtsB, FtsQ, FtsI, FtsN) in order to understand how they interact within the region of the cellular membrane. This project will begin to unravel the structural organization of the transmembrane region of the divisome and establish important groundwork needed for the development of new strategies for understanding and controlling bacterial growth.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM099752-02
Application #
8724521
Study Section
Biochemistry and Biophysics of Membranes Study Section (BBM)
Program Officer
Chin, Jean
Project Start
2013-09-01
Project End
2018-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Biochemistry
Type
Earth Sciences/Resources
DUNS #
City
Madison
State
WI
Country
United States
Zip Code
53715
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