About

Tatyana Igumenova is a professor in the Department of Biochemistry and Biophysics with a focus on signal transduction, membrane proteins, lipid membranes, lipid-activated kinases, and protein structure and dynamics. Her research centers on understanding the structural basis of signal transduction on membrane surfaces, studying protein systems that regulate key signaling events such as lipid- and calcium-dependent phosphorylation, neurotransmission, and conformational changes in proteins. Her laboratory employs an integrative structural biology approach, utilizing advanced solution Nuclear Magnetic Resonance (NMR) spectroscopy, X-ray crystallography, and atomistic molecular dynamics simulations of protein-membrane systems. Her expertise includes lipid signaling and its dysregulation in disease, membrane proteins, and structural biology techniques like NMR and X-ray crystallography. Igumenova's work has contributed to understanding the regulation and structure of Protein Kinase C, developing pharmaceutical approaches for targeting PKC in diseases such as cancer and Alzheimer’s, and exploring lipid transfer proteins as antifungal targets. She also investigates xenobiotic metal ions, their interactions with proteins, and their toxicity, employing in-cell NMR techniques. Additionally, her research includes studying the regulation of kinases by Pin1, a peptidyl-prolyl isomerase, revealing novel mechanisms of kinase regulation relevant to cancer. Her background includes a Ph.D. from Columbia University and postdoctoral work at the University of Pennsylvania and Columbia University.

Research topics

• Biochemistry
• Chemistry
• Biology
• Cell biology
• Materials science
• Computational biology
• Combinatorics
• Mathematics
• Biophysics
• Bioinformatics
• Chemical physics

Selected publications

• BPS2026 – An atomistic view of lipid exchange by Sec14-like phosphatidylinositol transfer proteins

  Biophysical Journal · 2026-02-01

  article1st authorCorresponding
  PublisherDOI

• In vitro methods for measuring lipid binding, transfer and competitive displacement reactions by peripheral membrane proteins

  Methods in enzymology on CD-ROM/Methods in enzymology · 2026-01-01

  book-chapterOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Introduction to solution state NMR spectroscopy

  Elsevier eBooks · 2026-01-01

  book-chapter1st authorCorresponding
  PublisherDOI

• A brief history of phosphatidylinositol transfer proteins: from the backwaters of cell biology to prime time in lipid signaling

  Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · 2025-05-10

  reviewOpen accessSenior author
  PublisherOA PDFDOI

• Molecular mechanism by which SARS-CoV-2 Orf9b suppresses the Tom70-Hsp90 interaction to evade innate immunity

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-18 · 2 citations

  preprintOpen access

  Abstract The Tom70-Hsp90 interaction is critical for activating MAVS-mediated interferon (IFN) production. Upon RNA virus infection, cytosolic Hsp90 recruits key innate immune signaling proteins to MAVS on mitochondria through its interaction with Tom70. To evade this innate immune response, the SARS-CoV-2 protein Orf9b binds to Tom70, thereby disrupting the Tom70-Hsp90 interaction and suppressing IFN production. Despite its importance, the molecular mechanism underlying Orf9b-mediated inhibition of IFN signaling remains unclear. Here, using an integrative approach combining cryo-electron microscopy, 19 F NMR spectroscopy, and isothermal titration calorimetry (ITC), we show that Orf9b inhibits Hsp90 binding to Tom70 through a bipartite mechanism. The helix and intrinsically disordered tail of Orf9b sterically block the access of two distinct structural units of Hsp90 to Tom70. We also find that Orf9b-mediated allosteric conformational changes in Tom70 do not contribute to the inhibition of the Hsp90 binding. Comprehensive structural, thermodynamic, and kinetic analyses further reveal that Orf9b primarily slows the association kinetics between Hsp90 and Tom70. Collectively, our results provide a high-resolution mechanistic framework for understanding Orf9b-mediated suppression of the host innate immune response.

  PublisherDOI

• Crystal Structure of a ternary complex of Saccharomyces cerevisiae Sec14 with a small molecule inhibitor and phosphatidylcholine

  2025-10-23

  dataset
  PublisherDOI

• Abstract 2061 The mechanistic basis for immune evasion by Orf9b of SARS-CoV-2

  Journal of Biological Chemistry · 2024-03-01

  articleOpen access

  The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is considered the worst pandemic of the 21st century. Despite the successes in vaccine production and treatment, there remains an urgent need to understand how SARS-CoV-2 evades the innate immune system to prevent future outbreaks. An accessory protein of SARS-CoV-2, open reading frame 9b (Orf9b), is a crucial antagonist of the antiviral response. Orf9b binds to the translocase of mitochondrial outer membrane 70 (Tom70), preventing the interaction of Tom70 with heat shock protein 90 (Hsp90). This inhibition subsequently blocks the interferon response against SARS-CoV-2. However, despite its importance, the molecular mechanism of how Orf9b inhibits the Tom70-Hsp90 interaction remains unclear. Whereas Orf9b binds to the hydrophobic pocket in the C-terminal domain of Tom70, Hsp90 is thought to interact with the N-terminal domain of Tom70 through its EEVD motif. To elucidate the structural basis of this mechanism, we employ single particle cryo-electron microscopy (cryo-EM) and fluorine-19 nuclear magnetic resonance spectroscopy (19F NMR). In combination with other biophysical approaches, such as isothermal titration calorimetry (ITC) and biolayer interferometry (BLI), we reveal the structural basis by which Orf9b inhibits the binding of Tom70 to Hsp90. Our results demonstrate the mechanistic basis for the competitive binding of Orf9b and Hsp90 to Tom70. We expect that our results will provide mechanistic insights into how SARS-CoV-2 inhibits the host innate immune response through Tom70 antagonization. This project was funded by the Welch Foundation (Grant No. A-2028-20230405).

  PublisherOA PDFDOI

• A novel bivalent interaction mode underlies a non-catalytic mechanism for Pin1-mediated protein kinase C regulation

  eLife · 2024-04-09 · 4 citations

  articleOpen accessSenior author

  Regulated hydrolysis of the phosphoinositide phosphatidylinositol(4,5)-bis-phosphate to diacylglycerol and inositol-1,4,5-P 3 defines a major eukaryotic pathway for translation of extracellular cues to intracellular signaling circuits. Members of the lipid-activated protein kinase C isoenzyme family (PKCs) play central roles in this signaling circuit. One of the regulatory mechanisms employed to downregulate stimulated PKC activity is via a proteasome-dependent degradation pathway that is potentiated by peptidyl-prolyl isomerase Pin1. Here, we show that contrary to prevailing models, Pin1 does not regulate conventional PKC isoforms α and βII via a canonical cis-trans isomerization of the peptidyl-prolyl bond. Rather, Pin1 acts as a PKC binding partner that controls PKC activity via sequestration of the C-terminal tail of the kinase. The high-resolution structure of full-length Pin1 complexed to the C-terminal tail of PKCβII reveals that a novel bivalent interaction mode underlies the non-catalytic mode of Pin1 action. Specifically, Pin1 adopts a conformation in which it uses the WW and PPIase domains to engage two conserved phosphorylated PKC motifs, the turn motif and hydrophobic motif, respectively. Hydrophobic motif is a non-canonical Pin1-interacting element. The structural information combined with the results of extensive binding studies and experiments in cultured cells suggest that non-catalytic mechanisms represent unappreciated modes of Pin1-mediated regulation of AGC kinases and other key enzymes/substrates.

  PublisherDOI

• Author response: A novel bivalent interaction mode underlies a non-catalytic mechanism for Pin1-mediated protein kinase C regulation

  2024-03-12

  peer-reviewOpen accessSenior author

  Integrated biophysical, structural, and in-cell approaches demonstrate a non-canonical and non-isomerizable binding motif-dependent mode of protein kinase C regulation by the peptidyl-prolyl isomerase Pin1 in mammalian cells.

  PublisherDOI

• Protein-Cadmium Interactions in Crowded Biomolecular Environments Probed by In-cell and Lysate NMR Spectroscopy

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-11-05 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract One of the mechanisms by which toxic metal ions interfere with cellular functions is ionic mimicry, where they bind to protein sites in lieu of native metals Ca 2+ and Zn 2+ . The influence of crowded intracellular environments on these interactions is not well understood. Here, we demonstrate the application of in-cell and lysate NMR spectroscopy to obtain atomic-level information on how a potent environmental toxin cadmium interacts with its protein targets. The experiments, conducted in intact E. coli cells and their lysates, revealed that Cd 2+ can profoundly affect the quinary interactions of its protein partners, and can replace Zn 2+ in both labile and non-labile protein structural sites without significant perturbation of the membrane binding function. Surprisingly, in crowded molecular environments Cd 2+ can effectively target not only all-sulfur and mixed sulfur/nitrogen but also all-oxygen coordination sites. The sulfur-rich coordination environments show significant promise for bioremedial applications, as demonstrated by the ability of the designed protein scaffold α 3 DIV to sequester intracellular cadmium. Our data suggests that in-cell NMR spectroscopy is a powerful tool for probing interactions of toxic metal ions with their potential protein targets, and for the assessment of potency of sequestering agents.

  PublisherOA PDFDOI

Recent grants

• Mechanisms of signal transduction revealed through unique chemistry of xenobiotic metal ions

  NSF · $500k · 2019–2023

• CAREER: Biological chemistry of Pb2+ revealed through Pb2+ mediated protein-membrane interactions

  NSF · $550k · 2012–2018

• Structural and Functional Studies of Protein Kinase C Regulation

  NIH · $3.3M · 2014–2029

• NIH Grant F32GM071133

  NIH · $55k · 2007

Frequent coauthors

• A. Joshua Wand

  Texas A&M University

  42 shared

• Sachin Katti

  Texas A&M University

  29 shared

• Ann E. McDermott

  Columbia University

  27 shared

• Eric K. Paulson

  Yale University

  16 shared

• Rachel W. Martin

  University of Oxford

  16 shared

• Kendra K. Frederick

  The University of Texas Southwestern Medical Center

  16 shared

• Kurt W. Zilm

  Yale University

  16 shared

• Bin Her

  Texas A&M University

  16 shared

Education

• Ph.D.

  Columbia University

  2003

• Other

  University of Pennsylvania

  2005

• Other

  Columbia University

  2007