This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The function of diphtheria toxin T-domain (DTT) is to translocate the catalytic domain of the toxin across the lipid bilayer in response to acidification of the endosome, a mode of entry shared by a number of bacterial toxins, including the potential bioweapon botulinum. Despite the progress in characterization of membrane interactions of DTT, the molecular mechanism of its action and the structure of DTT in its functional membrane-inserted form remain unknown. Hemifluorinated compounds, such as HF-TAC, are a novel class of non-detergent surfactants designed to amend solubilization of membrane proteins for functional and structural studies. Because DTT, depending on pH, can be found in both an insertion-competent and water-soluble form, it presents a convenient model for studying the general effects of these surfactants on the membrane protein insertion/folding pathway. The objective of this grant is to determine the mode of interaction of surfactants with DTT using site-directed fluorescence labeling and other spectroscopic approaches.
The specific aims are: (1) determine the effect of HF-TAC on the aggregation state of DTT; (2) determine the effect of HF-TAC on the free energy of membrane association of DTT; (3) determine the effect of HF-TAC on DTT-induced membrane disruption; (4) determine the direct effect of HF-TAC on the integrity of the lipid vesicles. This study will lay the groundwork for subsequent high resolution structural studies of DTT in membrane environment.
|He, Chenchen; Duan, Shaofeng; Dong, Liang et al. (2017) Characterization of a novel p110?-specific inhibitor BL140 that overcomes MDV3100-resistance in castration-resistant prostate cancer cells. Prostate 77:1187-1198|
|Li, Jiaqin; Wehmeyer, Graham; Lovell, Scott et al. (2016) 1.65?Å resolution structure of the AraC-family transcriptional activator ToxT from Vibrio cholerae. Acta Crystallogr F Struct Biol Commun 72:726-31|
|Ponnurangam, Sivapriya; Dandawate, Prasad R; Dhar, Animesh et al. (2016) Quinomycin A targets Notch signaling pathway in pancreatic cancer stem cells. Oncotarget 7:3217-32|
|Freitas, Natalia; Lukash, Tetyana; Dudek, Megan et al. (2015) Capacity of a natural strain of woodchuck hepatitis virus, WHVNY, to induce acute infection in naive adult woodchucks. Virus Res 205:12-21|
|Kumaraswamy, E; Wendt, K L; Augustine, L A et al. (2015) BRCA1 regulation of epidermal growth factor receptor (EGFR) expression in human breast cancer cells involves microRNA-146a and is critical for its tumor suppressor function. Oncogene 34:4333-46|
|Freitas, Natalia; Abe, Kenji; Cunha, Celso et al. (2014) Support of the infectivity of hepatitis delta virus particles by the envelope proteins of different genotypes of hepatitis B virus. J Virol 88:6255-67|
|Tang, Yuzhe; Chen, Ruibao; Huang, Yan et al. (2014) Natural compound Alternol induces oxidative stress-dependent apoptotic cell death preferentially in prostate cancer cells. Mol Cancer Ther 13:1526-36|
|Freitas, Natalia; Cunha, Celso; Menne, Stephan et al. (2014) Envelope proteins derived from naturally integrated hepatitis B virus DNA support assembly and release of infectious hepatitis delta virus particles. J Virol 88:5742-54|
|Grogan, Patrick T; Sarkaria, Jann N; Timmermann, Barbara N et al. (2014) Oxidative cytotoxic agent withaferin A resensitizes temozolomide-resistant glioblastomas via MGMT depletion and induces apoptosis through Akt/mTOR pathway inhibitory modulation. Invest New Drugs 32:604-17|
|Perchellet, Antoine L; Jasti, Susmita; Petroff, Margaret G (2013) Maternal CD4ýýý and CD8ýýý T cell tolerance towards a fetal minor histocompatibility antigen in T cell receptor transgenic mice. Biol Reprod 89:102|
Showing the most recent 10 out of 174 publications