TTUHSC School of Medicine
HomeSchool of MedicineCell Physiology and Molecular BiophysicsFacultyGuillermo Altenberg

Ongoing Projects

For the ongoing projects we use a variety of methodologies, including molecular biological (mutagenesis), biochemical (protein purification and reconstitution, production of nanodiscs), physiological (transport assays), biophysical (electrophysiology, photolysis kinetics, fluorescence, luminescence resonance energy transfer, light scattering), and structural (X-ray crystallography, cryo-electron microscopy) techniques.

  • Structure/function/inhibition of connexin hemichannels

Our connexin-related projects focus on hemichannels. We are interested in the structure of the hemichannels, their mechanism of regulation, and the discovery of new inhibitors for treatment of disorders associated with abnormal hemichannel activation.

Selected Publications

Krishnan S, Fiori MC, Whisenant TE, Cortes DM, Altenberg GA, Cuello LG. An Escherichia coli-based assay to assess the function of recombinant human hemichannels. SLAS Discov 22(2):135-143, 2017.

Fiori MC, Krishnan S, Cortes DM, Retamal MA, Reuss L, Altenberg GA, Cuello LG. Functional hemichannels formed by human connexin 26 expressed in bacteria. Biosci Rep 35(2): e00177, 2015.

Fiori MC, Reuss L, Cuello LG, Altenberg GA. Functional analysis and regulation of purified connexin hemichannels. Front Physiol. 5:71, 2014.

Fiori MC, Figueroa V, Zoghbi ME, Saéz JC, Reuss L, Altenberg GA. Permeation of calcium through purified connexin 26 hemichannels. J Biol Chem 287(48):40826-34, 2012.

Bao X, Lee SC, Reuss L, Altenberg GA. Change in permeant size selectivity by phosphorylation of connexin 43 gap-junctional hemichannels by PKC. Proc Natl Acad Sci USA 104(12):4919-24, 2007.

Chen Y, Deng Y, Bao X, Reuss L, Altenberg GA. Mechanism of the defect in gap-junctional communication by expression of a connexin 26 mutant associated with dominant deafness. FASEB J 19(11):1516-8, 2005.

Bao X, Reuss L, Altenberg GA. Regulation of purified and reconstituted connexin 43 hemichannels by protein kinase C-mediated phosphorylation of Serine 368. J Biol Chem 279(19):20058-66, 2004.

Bao X, Altenberg GA, Reuss L. Mechanism of regulation of the gap junction protein connexin 43 by protein kinase C-mediated phosphorylation. Am J Physiol Cell Physiol 286(3):C647-54, 2004.

  • Molecular mechanism of ATP-binding cassette (ABC) exporters

    Our general goal is to elucidate the conformational changes of ABC exporters at the molecular level during the transport cycle. In particular, our focus is on the movements of different domains in real time with Angstrom resolution with the proteins reconstituted in nanodiscs membranes.

Selected  Publications

Arana MR, Altenberg G. ATP-binding cassette exporters: structure and mechanism with a focus on P-glycoprotein and MRP1. Curr Med Chem, 2017. Epub ahead of print (PMID: 29022498).

Zoghbi ME, Mok L, Swartz DJ, Singh A, Fendley GA, Urbatsch IL, Altenberg GA. Substrate-induced conformational changes in the nucleotide-binding domains of lipid bilayer-associated P-glycoprotein during ATP hydrolysis. J Biol Chem, 2017. Epub ahead of print (PMID: 29018094).

Zoghbi ME, Altenberg GA. Luminescence resonance energy transfer spectroscopy of ATP-binding cassette proteins. Biochim Biophys Acta, 2017. Epub ahead of print (PMID: 28801111).

Zoghbi ME, Cooper RS, Altenberg GA. The lipid bilayer modulates the structure and function of an ATP-binding cassette exporter. J Biol Chem 291(9):4453-61, 2016.

Zoghbi ME, Altenberg GA. ATP binding to two sites is necessary for dimerization of nucleotide-binding domains of ABC proteins. Biochem Biophys Res Commun 443(1):97-102, 2014.

Zoghbi ME, Altenberg GA. Hydrolysis at one of the two nucleotide-binding sites drives the dissociation of ATP-binding cassette nucleotide-binding domain dimers. J Biol Chem 288(47):34259-65, 2013.

Cooper RS, Altenberg GA. Association/dissociation of the nucleotide-binding domains of the ATP-binding cassette protein MsbA measured during continuous hydrolysis. J Biol Chem 288(29):20785-96, 2013.

Zoghbi ME, Fuson KL, Sutton RB, Altenberg GA. Kinetics of the association/dissociation cycle of an ATP-binding cassette nucleotide-binding domain. J Biol Chem 287(6):4157-64, 2012.

  • Design, production and characterization of polymer nanodiscs

In recent years, nanodiscs have been introduced as a new approach for the study of membrane proteins in a lipid bilayer. They consist of two molecules of a membrane scaffold protein that encase a small patch of lipid bilayer. Our goal is to design and produce new types of nanodiscs where the membrane scaffold proteins and/or the lipid bilayer are replaced with synthetic copolymers, yielding new nanostructures with increased stability and chemical versatility.

Selected  Publications

Fiori MC, Jiang Y, Zheng W, Anzaldua M, Borgnia MJ, Altenberg GA, Liang H. Polymer nanodiscs: Discoidal amphiphilic block copolymer membranes as a new platform for membrane proteins. Sci Rep 7(1):15227, 2017.

Fiori MC, Jiang Y, Altenberg GA, Liang H. Polymer-encased nanodiscs with improved buffer compatibility. Sci Rep 7(1):7432, 2017. 

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