Protein translocation is one of the fundamental aspects of cell biology. Understanding how proteins move from their sites of synthesis to their sites of action is relevant since almost half of the proteins of a cell are transported into or across a membrane. In fact, the amounts and locations of particular proteins are controlled during development, during the cell cycle, and for maintenance of healthy cells, failure in secretion results in not only activity deficiency at the indeed subcellular location but also toxic levels of molecules in the wrong place. The long term objectives of the following proposal are to understand the molecular mechanisms by which cellular machinery translocates proteins across membrane. The current focus is on the early events that occurs in the E. coli Sec translocation system, with emphasis on mechanisms regarding (1) the binding of a polypeptide by a translocation dedicated chaperone SecB (2) the general recognition motif within the translocating polypeptide, and (3) the interaction of SecB with its membrane receptor SecA and the effect of polypeptide binding by SecB. Our approach will be to use high resolution X-ray crystallography to establish the three- dimensional structures of SecB and its relevant complexes with peptides and/or SecA. Mutational and biochemical experiments will then be used to complement structural studies. The combination of these approaches will help us to understand the physical chemistry that govern protein translocation by the Sec system.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM060997-03
Application #
6520191
Study Section
Biophysical Chemistry Study Section (BBCB)
Program Officer
Chin, Jean
Project Start
2000-03-01
Project End
2005-02-28
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
3
Fiscal Year
2002
Total Cost
$212,490
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Biochemistry
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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