Glycans are key biomolecules essential to the existence of all known living organisms. Besides their very well-known metabolic and structural roles, glycans are also involved in the regulation of essential cellular functions, by acting as ligands for the so-called lectins, which are carbohydrate-specific receptors. In our group, we study, from a molecular perspective, the rules governing these glycan-lectin interactions, with the aim of establishing structural-functional relationships that allow us to comprehend and modulate the biological events mediated by these molecular recognition processes. For that, we integrate different biophysical techniques, with a special emphasis on Nuclear Magnetic Resonance (NMR). Recent results related to Galectins and C-type lectins binding to different partners (glycans and glycoproteins), as well as new NMR strategies to approach complex binding systems will be presented.
References:
[1] Marta G. Lete, Antonio Franconetti, Sara Bertuzzi, Sandra Delgado, Mikel Azkargorta, Félix Elortza, Oscar Millet, Gonzalo Jiménez-Osés, Ana Arda, Jesús Jiménez-Barbero, NMR Investigation of Protein-Carbohydrate Interactions: The Recognition of Glycans by Galectins Engineered with Fluorotryptophan Residues, Chem. Eur J. 29(5), e202202208 (2023). https://doi.org/10.1002/chem.202202208.
[2] Sara Bertuzzi, Francesca Peccati, Sonia Serna, Raik Artschwager, Simona Notova, Michel Thépaut, Gonzalo Jiménez-Osés, Franck Fieschi, Niels C. Reichardt, Jesús Jiménez-Barbero, Ana Ardá, Immobilization of Biantennary N-Glycans Leads to Branch Specific Epitope Recognition by LSECtin, ACS Cent. Sci. 8(10), 1415-1423 (2022). https://doi.org/10.1021/acscentsci.2c00719.
[3] Luca Unione, María J Moure, Maria Pia Lenza, Iker Oyenarte, June Ereño-Orbea, Ana Ardá, Jesús Jiménez-Barbero, The SARS-CoV-2 Spike Glycoprotein Directly Binds Exogeneous Sialic Acids: A NMR View, Angew. Chem. Int. Ed. 61(18), e202201432 (2022). https://doi.org/10.1002/anie.202201432.
[4] María J. Moure, Ana Gimeno, Sandra Delgado, Tammo Diercks, Geert-Jan Boons, Jesús Jiménez-Barbero, Ana Ardá, Selective 13C-Labels on Repeating Glycan Oligomers to Reveal Protein Binding Epitopes through NMR: Polylactosamine Binding to Galectins, Angew. Chem. Int. Ed. 60 (34), 18777-18782 (2021). https://doi.org/ 10.1002/anie.202106056.
[5] Jon I. Quintana, Sandra Delgado, Reyes Núñez-Franco, F. Javier Cañada, Gonzalo Jiménez-Osés, Jesús Jiménez-Barbero, Ana Ardá, Galectin-4 N-Terminal Domain: Binding Preferences Toward A and B Antigens With Different Peripheral Core Presentations, Front Chem. 2021, 9, 664097 (2021). https://doi.org/10.3389/ fchem.2021.664097.
[6] Sara Bertuzzi, Ana Gimeno, Reyes Núñez-Franco, Ganeko Bernardo-Seisdedos, Sandra Delgado, Gonzalo Jiménez-Osés, Oscar Millet, Jesús Jiménez-Barbero, Ana Ardá, Unravelling the Time Scale of Conformational Plasticity and Allostery in Glycan Recognition by Human Galectin-1, Chem. Eur. J.26 (67), 15643-15653 (2020). https://doi.org/10.1002/chem.202003212.
[7] Ana Gimeno, Sandra Delgado, Pablo Valverde, Sara Bertuzzi, Manuel Alvaro Berbís, Javier Echavarren, Alessandra Lacetera, Sonsoles Martín-Santamaría, Avadhesha Surolia, Francisco Javier Cañada, Jesus Jiménez-Barbero, Ana Ardá, Minimizing the Entropy Penalty for Ligand Binding: Lessons from the Molecular Recognition of the Histo Blood-Group Antigens by Human Galectin-3, Angew. Chem. Int. Ed. 58 (22), 7268-7272 (2019). https://doi.org/10.1002/anie.201900723.
Ana Ardá is Ikerbasque Associate Principal Investigator at CICbioGUNE (Bilbao, Spain). Her research revolves around molecular recognition phenomena, in particular those involving glycans and glycan binding proteins, with the aim of understanding their molecular basis at the atomic level. Trained as a Chemist at the University of A Coruña (Spain) she got her PhD degree (2006) from the same university in Natural Products Chemistry. After a postdoc at the Bijvoet Center for Biological Research in Utrecht (Netherlands), where she started to work on Carbohydrates, she moved back to Spain (2008), to the Center for Biological Research (CIB-CSIC, Madrid). There she specialised in the use of NMR methods to understand and characterize glycan structural features as well as their molecular recognition by protein receptors. In 2014, she moved to CIC bioGUNE Research Center in Bilbao (Spain), where in 2015 was awarded with the Ramón y Cajal Fellow (tenure-track position), and in 2022 she was promoted to Ikerbasque Research Associate. At CIC bioGUNE she is involved in different projects where, by employing a combination of different chemical, biophysical and biomolecular techniques, with an emphasis on NMR, she tries to understand from a molecular perspective, how glycans bind to special protein receptors, mainly lectins and antibodies, in biologically relevant processes, mostly related to host-pathogen interactions and immune response.
