TEAD1 Mechanistic Insights through HDX-MS: iBET at International Conference on Hydrogen Deuterium Exchange MS
Enabling Mode of Action Studies of TEAD1 Ligands through Hydrogen Deuterium Exchange Mass-Spectrometry and Tailored Protein Purification Workflows
On March 9-13, iBET scientists participated in the 5th International Conference on Hydrogen Deuterium Exchange Mass Spectrometry (HDX-MS 2026), held in Strasbourg, France.
Representing iBET was Alessio Bortoluzzi and Catarina Malta (from the Merck Satellite Lab), who contributed to the scientific program with a flash presentation and poster. Also attending was Dr. Joerg Bomke, Principal Scientist and HDX-MS specialist at Merck KGaA, and long-term collaborator of iBET.
Enabling Mode of Action Studies of TEAD1 Ligands through Hydrogen Deuterium Exchange Mass-Spectrometry and Tailored Protein Purification Workflows
The team presented work aimed at deciphering the molecular mechanisms by which lipidic and synthetic ligands modulate TEAD1.
Catarina Malta, Joerg Bomke and Alessio Bortoluzzi presenting the poster. Alessio presenting the corresponding flash presentation.
TEAD1-4 proteins, central transcription factors in the Hippo signalling pathway, play a fundamental role in controlled cell proliferation, tissue homeostasis and organ size. Because dysregulation of the Hippo pathway is associated with cancer, TEAD proteins have emerged as promising yet complex therapeutic targets.
Much of the ongoing drug-discovery effort focuses on disrupting the interaction between TEAD1-4 and their cognate transcriptional co-activator proteins YAP and TAZ.
This work highlighted:
- How HDX-MS, combined with tailored protein-purification strategies, enables mechanistic insights into TEAD1 modulation by lipidic and synthetic P-site ligands;
- How distinct P-site binders influence TEAD1 conformational dynamics and impact the structural behaviours or TEAD1/YAP interfaces;
- Experimental strategies and technical considerations required to generate TEAD1 samples suitable for probing protein dynamics under different P-site ligands.
Together, these findings illustrate how protein dynamic characterization can elucidate mechanisms of TEAD1 regulation and support the development of effective Hippo-pathway therapeutics.
iBET’s participation in HDX-MS 2026 reflects the institute’s dedication to advancing integrative structural biology, supporting pharmaceutical development, and strengthening its visibility within the international HDX-MS community.
