HIV-1 proteins and their complexes with host proteins

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Human immunodeficiency virus type 1 (HIV-1) affects approximately 40 million people globally, including 1.2 million in the USA and over 100,000 in Texas. Although studied extensively, many mechanisms by which HIV-1 manipulates host cell pathways remain unclear. This project aims to clarify how key HIV-1 proteins interact with host proteins to influence viral trafficking and modify host processes. The insights gained will support pharmaceutical development targeting these protein complexes and enhance our understanding of HIV-1–host interactions. It will also contribute to the general knowledge about protein complexes

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Publications

(1) Insights into the oligomeric structure of the HIV-1 Vpu protein (2023), J Struct Biol, 215, S. Majeed, O. Adetuyi, P. P. Borbat, Md M. Islam, O. Ishola, B. Zhao, E. R. Georgieva*

(2) HIV-1 Vpu protein forms stable oligomers in aqueous solution via its transmembrane domain self-association (2023), Sci Rep, S. Majeed#, L. Dang#, Md M. Islam, O. Ishola, P. P. Borbat, S. J. Ludtke*, E. R. Georgieva*

(3) The soluble state of the HIV-1 Vpu protein forms a complex with Ca2+-calmodulin (2026), Prot Sci, 35, O. Ishola, Md M. Islam, E. Hadadianpour, P. P. Borbat, A. Ogunbowale, J. C. R. Amador, E. R. Georgieva*

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Virus encoded small membrane proteins

Coupling protein’s inherent conformational plasticity with host membranes’ properties to control cellular processes

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The focus is on small viral proteins, which reside and function in cellular membranes of infected cells. These proteins consist of 80-120 amino acid residues with one or two transmembrane (TM) helices. They have the ability to form oligomers with ion-conducting channel or pore activities; they also play a role in virus budding.

   The Georgieva lab studies the influenza A M2 (IAM2), HIV-1 Vpu, HCV p7, and human T-cell leukemia virus 1 (HTCLV-1) p13II proteins in lipid environments aiming to understand the mechanisms of assembly of these proteins’ oligomers and link the oligomeric structures to the proteins’ ability to act as ion channels/pores or destabilize the membrane and increase its permeability to ions. 

   Our studies will deliver significant biological insights and will have substantial broader impacts on the field of membrane biology because it will uncover important novel details of how small viral membrane proteins efficiently utilize the cellular membranes for their function; It will markedly expand our understanding of protein-lipid interactions in general.

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Publications

(1) Highly versatile small virus-encoded proteins in cellular membranes: A structural perspective on how proteins’ inherent conformational plasticity couples with host membranes’ properties to control cellular processes (2025), J Struct Biol X, 11, A. Saffarian Delkhosh, E. Hadadianpour, Md M. Islam, E. R. Georgieva*

(2) Conformations of influenza A M2 protein in DOPC/DOPS and E. coli native lipids and proteins (2024), Biophys J, 123,  G. Sanders, P. P. Borbat and E. R. Georgieva**
(3) Conformational response of influenza A M2 transmembrane domain to amantadine drug binding at low pH (pH 5.5) (2016) Front Physiol, 7:317. E. R. Georgieva*, P. P. Borbat, K. Grushin, S. Stoilova-McPhie, N. J. Kulkarni, Z. Liang, J. H. Freed*
(4) Mechanism of influenza A M2 transmembrane domain assembly in lipid membranes (2015) Sci Rep, 5, 11757. E. R. Georgieva*, P. P. Borbat, H. D. Norman and J.H. Freed*
(5) High-yield production in E. coli and characterization of full-length functional p13II protein from human T-cell leukemia virus type 1 (2020), Prot Expr Purif, 173:105659. E. R. Georgieva*, P. P. Borbat, C. Fanouraki, J. H. Freed

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