Tai, Phang - Georgia State University

个人简介

Ph.D. Microbiology University of California-Davis 1969 MGB/Microbial Physiology and Genetics: Protein Export The current aim of this laboratory is to understand the molecular mechanisms of protein secretion and export across membranes in bacteria. The major approach is to combine genetic manipulation and biochemical studies in an in vitro protein translocation system developed earlier in this laboratory. Schematic representations of the integral forms of SecA (As and Am), and how these two forms comprise the major portion of the secretory channel embedded within the cytoplasmic membrane of Echerichia coli. (A) SecA potentially forming two types of channels, with and without SecYEG. (B) Our working model for SecA as the principal protein conducting-channel. (C) TEM ring-structures of SecA by single particle analyses Most protein export in Escherichia coli utilizes a signal-peptide dependent pathway that involves with the gene products of several sec genes as well as signal peptidases. Our project analyzes the translocation of periplasmic and outer membrane proteins. Several approaches are being used to analyze the functions of SecA and other Sec proteins in the process, in particular in relation to the ATP hydrolysis that is essential for the protein export. Genetic manipulation allows the overproduction of the Sec proteins, and purified proteins are used for reconstitution of the functional membrane vesicles and translocation system. Conversely, membranes deficient in Sec proteins are used to analyze the effects in translocation. Our recent work suggests that SecE/SecY are not obligatory for translocation of certain precursor proteins. Moreover, SecA has, in addition to being a major component of essential ATPase, also performs an important structural role in protein translocation. Current work focuses on examining the structure and function(s) of SecA as an integral protein -conducting channel, and determines the roles of SecYEG in the process. Electrophysiological studies, and election microscopic and atomic force microscopic studies are carried out to complement the biochemical studies. Another project investigates the export of Colicin V, which does not contain a typical signal peptide and does not rely on the Sec-dependent system. Instead, the export of Colicin V, in addition to TolC, requires the products of two additional genes that constitute the pathway for extracellular export. One of these, cvaB, codes for a membrane protein possesses domains, including ATP binding sites, similar to the transporters for multi-drug resistance and cystic fibrosis chloride channel. Recent work has focused on the protease function and nucleotide specificity of the CvaB protein.

研究领域

Molecular Genetics and Biochemistry Research Group Applied & Environmental Microbiology Research Group Microbial Physiology and Genetics: Protein Export

近期论文

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Dissecting structures and functions of SecA-only protein-conducting channels: ATPase, pore structure, ion channel activity, protein translocation, and interaction with SecYEG/SecDF•YajC. Hsieh YH, Huang YJ, Zhang H, Liu Q, Lu Y, Yang H, Houghton J, Jiang C, Sui SF, Tai PC. PLoS One. 2017 Jun 2;12(6):e0178307. doi: 10.1371/journal.pone.0178307. eCollection 2017. Biphasic actions of SecA inhibitors on Prl/Sec suppressors: Possible physiological roles of SecA-only channels. Hsieh YH, Zhang H, Jin J, Dai C, Jiang C, Wang B, Tai PC. Biochem Biophys Res Commun. 2017 Jan 8;482(2):296-300. doi: 10.1016/j.bbrc.2016.11.057. Epub 2016 Nov 14. Using Chemical Probes to Assess the Feasibility of Targeting SecA for Developing Antimicrobial Agents against Gram-Negative Bacteria. Jin J, Hsieh YH, Cui J, Damera K, Dai C, Chaudhary AS, Zhang H, Yang H, Cao N, Jiang C, Vaara M, Wang B, Tai PC. ChemMedChem. 2016 Nov 21;11(22):2511-2521. doi: 10.1002/cmdc.201600421. Epub 2016 Oct 18. Meningioangiomatosis: A Disease With Many Radiological Faces. Nascimento FA, Kiehl TR, Tai PC, Valiante TA, Krings T. Can J Neurol Sci. 2016 Nov;43(6):847-849. Epub 2016 Sep 9. No abstract available. Inhibition and Dispersal of Pseudomonas aeruginosa Biofilms by Combination Treatment with Escapin Intermediate Products and Hydrogen Peroxide. Santiago AJ, Ahmed MN, Wang SL, Damera K, Wang B, Tai PC, Gilbert ES, Derby CD. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5554-62. doi: 10.1128/AAC.02984-15. Print 2016 Sep. Design, Synthesis and Evaluation of Triazole-Pyrimidine Analogues as SecA Inhibitors. Cui J, Jin J, Chaudhary AS, Hsieh YH, Zhang H, Dai C, Damera K, Chen W, Tai PC, Wang B. ChemMedChem. 2016 Jan 5;11(1):43-56. doi: 10.1002/cmdc.201500447. Epub 2015 Nov 26. Evaluation of small molecule SecA inhibitors against methicillin-resistant Staphylococcus aureus. Jin J, Cui J, Chaudhary AS, Hsieh YH, Damera K, Zhang H, Yang H, Wang B, Tai PC. Bioorg Med Chem. 2015 Nov 1;23(21):7061-8. doi: 10.1016/j.bmc.2015.09.027. Epub 2015 Sep 21. Meningitis and Reversible Cerebral Vasoconstriction Syndrome During the Postpartum Period. Boulos MI, Wortsman J, Swartz RH, Tai PC, Casaubon LK, Lazarou J. Can J Neurol Sci. 2015 Sep;42(5):341-3. doi: 10.1017/cjn.2015.268. Epub 2015 Aug 19. No abstract available.