Post by Christoph Rademacher
Professor for Molecular Drug Targeting at the University of Vienna and Max F. Perutz Labs and Co-Founder of Cutanos GmbH
Happy to share our latest paper uncovering a previously unrecognized allosteric regulatory mechanism in the human C-type lectin DC-SIGN. Together with Jonathan Lefèbre, Maurice Besch, Marcelo Daniel Gamarra, Jan-Oliver Kapp-Joswig, Annika Balke, Stevan Aleksic, Ph.D., Henry Flatau, Gregor Suchy, Elena Georgieva, Patrick Scheerer, Bettina G. Keller and Carlos Modenutti, we identify and characterize for the first time a cryptic allosteric pocket as a actionable regulatory element in a glycan-binding C-type lectin. Key insights • A gatekeeper residue (M270) controls access to a cryptic allosteric pocket • Pocket occupancy propagates through a hierarchical network to remodel the extended carbohydrate binding site • Glycan affinity is tuned without perturbing Ca²⁺ coordination at the canonical site • Mutations mimicking pocket occupation or exposure shift the carbohydrate recognition domain between low- and high-affinity states Open access: https://lnkd.in/deWU9-Rc Thanks to MSCA ITN ALLODD Allostery in Drug Discovery
