More than 30% of the proteins in all living cells must be transported across or integrated into a membrane, and many of the factors that promote protein insertion are essential for cell viability. Bacteria use two pathways to promote protein insertion into the plasma membrane. The Sec machinery is responsible for inserting the majority of the proteins into the membrane after targeting by the SRP/FtsY components. However, there is also a class of proteins that insert independent of the Sec machinery. These proteins require a novel protein called YidC, which was discovered in the year 2000. YidC is essential for bacterial cell growth, and is evolutionary conserved with homologs in mitochondria and chloroplasts. YidC also works with the Sec machinery to mediate membrane protein insertion. For Sec-dependent proteins, YidC has been proposed to play a role in the lateral transfer of membrane proteins into the lipid bilayer and to function as an assembly site to promote folding of transmembrane domains of membrane proteins. The goal of this research is to understand the exact role of YidC in membrane protein biogenesis. We plan to pursue the following specific aims: (1) Determine the substrate specificity of YidC; (2) Identify the substrate binding region and the organization of the transmembrane domains within the YidC protein; (3) Determine the relationship between YidC, SecYEG, ribosome, SRP/FtsY, and the proteins involved in membrane protein integration; and (4) Determine the function of YidC in membrane protein biogenesis. These studies should impact the field of bacterial membrane protein biogenesis and advance the knowledge of analogous pathways in eukaryotic cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM063862-07
Application #
7231955
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Chin, Jean
Project Start
2001-06-01
Project End
2009-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
7
Fiscal Year
2007
Total Cost
$248,068
Indirect Cost
Name
Ohio State University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Wang, Peng; Dalbey, Ross E (2011) Inserting membrane proteins: the YidC/Oxa1/Alb3 machinery in bacteria, mitochondria, and chloroplasts. Biochim Biophys Acta 1808:866-75
Stiegler, Natalie; Dalbey, Ross E; Kuhn, Andreas (2011) M13 procoat protein insertion into YidC and SecYEG proteoliposomes and liposomes. J Mol Biol 406:362-70
Dalbey, Ross E; Wang, Peng; Kuhn, Andreas (2011) Assembly of bacterial inner membrane proteins. Annu Rev Biochem 80:161-87
Belin, Dominique (2010) In vivo analysis of protein translocation to the Escherichia coli periplasm. Methods Mol Biol 619:103-16
Wang, Peng; Kuhn, Andreas; Dalbey, Ross E (2010) Global change of gene expression and cell physiology in YidC-depleted Escherichia coli. J Bacteriol 192:2193-209
Yuan, Jijun; Zweers, Jessica C; van Dijl, Jan Maarten et al. (2010) Protein transport across and into cell membranes in bacteria and archaea. Cell Mol Life Sci 67:179-99
Wang, Peng; Dalbey, Ross E (2010) In vitro and in vivo approaches to studying the bacterial signal peptide processing. Methods Mol Biol 619:21-37
Celebi, Nil; Dalbey, Ross E; Yuan, Jijun (2008) Mechanism and hydrophobic forces driving membrane protein insertion of subunit II of cytochrome bo 3 oxidase. J Mol Biol 375:1282-92
Klenner, Christian; Yuan, Jijun; Dalbey, Ross E et al. (2008) The Pf3 coat protein contacts TM1 and TM3 of YidC during membrane biogenesis. FEBS Lett 582:3967-72
Dong, Yuxia; Palmer, Sara R; Hasona, Adnan et al. (2008) Functional overlap but lack of complete cross-complementation of Streptococcus mutans and Escherichia coli YidC orthologs. J Bacteriol 190:2458-69

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