Umesh Bageshwar, PhD
Education and Post-Graduate Training
Dr. Umesh Bageshwar is an assistant professor-research of Molecular & Cellular Medicine. He received his BS in biology (1987) from the University of New Delhi and master’s degree with Distinction in bio sciences (1989) from JMI University, India. He earned his PhD in bio-sciences (1995) while working on “Biological Nitrogen Fixation in Azotobacter vinelandii,” from JMI University under the supervision of Professor H.K. Das (Jawaharlal Nehru Univ., New Delhi) and Professor M. Amin (JMI Univ., New Delhi). Later, he joined Professor Ada Zamir’s laboratory (1996-99) as a visiting scientist at the Weizmann Institute and worked on “Mechanisms of Halotolerance in a Green Alga Dunaliella salina.” From 1999 to 2003, he was a postdoctoral research associate in the Department of Horticultural Science at the Institute of Plant Genomics and Biotechnology at Texas A&M University. He worked as an associate research scientist in the laboratory of Dr. Siegfried Musser at the Texas A&M University Health Science Center from 2003 to 2011, before joining the Texas A&M faculty in 2011. His research focuses on the transport of folded proteins across bacterial cell membranes by the Twin Arginine Translocation (Tat) pathway.
Protein targeting and transport across lipid bilayers is a fundamental energy-requiring process in all organisms. Most exported bacterial proteins are transported using the conserved Sec translocation pathway. However, a distinct set of proteins are transported in fully folded and assembled form by the Tat pathway. These proteins are characterized by a twin-arginine-containing consensus motif (SRRxFLK) present in the N-terminal signal peptide of precursor proteins. The E. coli Tat translocation system contains four identified protein components: TatA, TatB, TatC, and TatE. However, mutational analyses have shown that a functional Tat system minimally requires TatB, TatC, and either TatA or TatE.
The Tat system was first identified in plant thylakoids as a translocation system that requires the proton motive force (PMF), and not ATP, for transport. From early experiments on thylakoids, it was concluded that the Tat system is energetically driven by the ΔpH alone. We reported the first efficient in vitro assay for the E. coli Tat machinery using purified overexpressed precursors and inverted membrane vesicles (IMVs) and demonstrated that the Δψ alone was sufficient to drive E. coli Tat transport. Further, we showed that two distinct Δψ-dependent steps are required for Tat transport. Interestingly, we did not detect a role for the ΔpH in influencing transport efficiency. We also showed a linear relationship between the hydrophobicity of the Tat signal peptide and in vitro translocation efficiency.
Current work focuses on identifying the interaction site(s) between the Tat precursor pre-SufI and the TatBC receptor complex based on chemical crosslinking and the complementation of the Escherichia coli Tat pathway by the Mycobacterium tuberculosis Tat pathway.
- Whitaker N., Bageshwar U.K. and Musser S.M. 2013. Effect of cargo size and shape on the transport efficiency of the bacterial Tat translocase. FEBS Lett. 587: 912-916.
- Liang F.C., Bageshwar U.K. and Musser S.M. 2012. Position-dependent effects of poly-lysine on Sec protein transport. J. Biol. Chem. 287:12703-12714.
- Whitaker N., Bageshwar U.K. and Musser S.M. 2012. Kinetics of precursor interaction with the bacterial Tat translocase detected by real-time FRET. J. Biol. Chem. 287: 11252-11260.
- Bageshwar U.K., Whitaker N., Fu-Cheng L., and Musser S.M. 2009. Interconvertibility of lipid- and translocon-bound forms of the bacterial Tat precursor pre-SufI. Mol. Microbiol. 74,209-226.
- Liang F.C., Bageshwar U.K., and Musser S.M. 2009. Bacterial Sec protein transport is rate- limited by precursor length: A single turnover study. Mol. Biol. Cell. 20, 4256-4266.
- Bageshwar U.K. and Musser S.M. (2007) Two electrical potential-dependent steps are required for transport by the Escherlchia coli Tat machinery. J. Cell Biol. 179, 87-99.
- Premkumar L., Greenblatt H.M., Bageshwar U.K., Savchenko T., Gokhman I., Sussman J.L. and Zamir A. 2005. Molecular adaptation to shifting environments: from the 3D structure of a salt-tolerant algal carbonic anhydrase to the predicted halotolerance of a mammalian isozyme. Proc. Natl. Acad. Sci., USA, 102, 7493-7498.
- Bageshwar U.K., Taneja-Bageshwar S., Moharram H.M., and Binzel M.L. 2005. Two isoforms of the A subunit of the vacuolar H+-ATPase in Lycopersicon esculentum: highly similar proteins but divergent patterns of tissue localization. Planta 220, 632-643.
- Bageshwar U.K., Premkumar L., Gokhman I., Savchenko T., Sussman J.L., and Zamir A. 2004. Natural Protein Engineering: a uniquely salt-tolerant, but not halophilic α-type carbonic anhydrase from algae proliferating in low- to hyper-saline environments. Protein Engineering, Design & Selection 17, 191-200.
- Bageshwar U.K., Raina R., and Das H.K. 1998. Characterization of a spontaneous mutant of Azotobacter vinelandii in which vanadium dependent nitrogen fixation is not inhibited by molybdenum. FEMS Microbiol. Lett. 162, 161-167.
- Bageshwar U.K., Raina R., Chaudhary N.R., and Das H.K. 1998. Analysis of upstream activation of the vnfH promoter in Azotobacter vinelandii. Can. J. Microbiol. 44, 405-415.