The PI's laboratory has recently identified five trans-acting regulatory factors governing prokaryotic gene expression in response to changes in oxygen tension and light intensity. During the proposed funding period, each of these regulatory factors will be genetically and biochemically characterized for their role in controlling gene expression in response to oxygen and light. Two """"""""oxygen responding"""""""" regulatory proteins contain sequence motifs indicating that they are membrane spanning sensor kinases that transmits information about anaerobioses via phosphorylation of a DNA binding response regulator. Each of these sensor kinases have sequence motifs indicating that they may be involved in forming an oxygen labile iron sulfur complex. The role of iron binding in kinase function will be probed by performing site directed mutagenesis on critical iron binding ligands as well as by EPR analysis of isolated polypeptides. One of these sensor kinases (SenC) is also structurally similar to the ScoI protein in yeast mitochondria which is known to be involved in assembly of cytochrome c oxidase. As is observed in yeast, mutations in SenC leads to a reduction in cytochrome c oxidase synthesis. It should be noted that in humans the failure to properly synthesize a functional cytochrome c oxidase complex has been implicated in degenerative diseases such as Parkinson's and Ischemic heart disease. An additional regulatory protein (HvrA) has been identified which is responsible for controlling gene expression in response to changes in light intensity. The light sensing capabilities of this protein will be analyzed by assaying for flavin binding capabilities of HvrA. The laboratory is also characterizing a light sensing regulatory protein involved in controlling expression of the enzyme S-adenosyl homocysteine hydrolase (SAHase). In humans, SAHase is an important contributing factor in the cytotoxic effects of adenosine leading to severe immune deficiency in patents with adenosine deaminase (ADA) deficiency.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM040941-06
Application #
2180631
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1989-12-01
Project End
1997-11-30
Budget Start
1993-12-01
Budget End
1994-11-30
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Indiana University Bloomington
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
Fang, Mingxu; Bauer, Carl E (2018) Regulation of stringent factor by branched-chain amino acids. Proc Natl Acad Sci U S A 115:6446-6451
Yamamoto, Haruki; Fang, Mingxu; Dragnea, Vladimira et al. (2018) Differing isoforms of the cobalamin binding photoreceptor AerR oppositely regulate photosystem expression. Elife 7:
Kumka, Joseph E; Schindel, Heidi; Fang, Mingxu et al. (2017) Transcriptomic analysis of aerobic respiratory and anaerobic photosynthetic states in Rhodobacter capsulatus and their modulation by global redox regulators RegA, FnrL and CrtJ. Microb Genom 3:e000125
Fang, Mingxu; Bauer, Carl E (2017) The Vitamin B12-Dependent Photoreceptor AerR Relieves Photosystem Gene Repression by Extending the Interaction of CrtJ with Photosystem Promoters. MBio 8:
Shimizu, Takayuki; Shen, Jiangchuan; Fang, Mingxu et al. (2017) Sulfide-responsive transcriptional repressor SqrR functions as a master regulator of sulfide-dependent photosynthesis. Proc Natl Acad Sci U S A 114:2355-2360
Cheng, Zhuo; Yamamoto, Haruki; Bauer, Carl E (2016) Cobalamin's (Vitamin B12) Surprising Function as a Photoreceptor. Trends Biochem Sci 41:647-650
Schindel, Heidi S; Bauer, Carl E (2016) The RegA regulon exhibits variability in response to altered growth conditions and differs markedly between Rhodobacter species. Microb Genom 2:e000081
Shimizu, Takayuki; Cheng, Zhuo; Matsuura, Katsumi et al. (2015) Evidence that Altered Cis Element Spacing Affects PpsR Mediated Redox Control of Photosynthesis Gene Expression in Rubrivivax gelatinosus. PLoS One 10:e0128446
Kumka, Joseph E; Bauer, Carl E (2015) Analysis of the FnrL regulon in Rhodobacter capsulatus reveals limited regulon overlap with orthologues from Rhodobacter sphaeroides and Escherichia coli. BMC Genomics 16:895
Vermeulen, Arjan J; Bauer, Carl E (2015) Members of the PpaA/AerR Antirepressor Family Bind Cobalamin. J Bacteriol 197:2694-703

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