New publication for Dr. Jesus Angulo
High-resolution NMR spectroscopy reveal details of the interactions of langerin, an important protein that constitutes a natural barrier against HIV-1.
Dr. Jesus Angulo, in an international collaboration with the Instituto de Investigaciones Quimicas of the Spanish National Research Council (IIQ-CSIC), in Seville (Spain), and the Institut de Biologie Structurale (IBS-CNRS), and CERMAV-CNRS, in Grenoble (France), has published his recent work in the Journal of the American Chemical Society. In the study, the research team have used Nuclear Magnetic Resonance (NMR) spectroscopy, cross-linking experiments, and computational techniques to characterize at atomic detail the molecular interactions between heparin and langerin, a pathogen receptor present on the surface of the Langerhans cells, which constitutes a natural barrier for HIV-1 infection. These cells are present in the mucosal lining of human genitalia and constitute the first obstacle that the HIV-1 finds in its way to infecting the host. Langerin had been previously demonstrated to be a fundamental player on the formation of the so-called Birbeck granules, the supramolecular structures that are responsible for the internalization and final elimination of the HIV-1 particles. Dr. Angulo and co-workers demonstrated the existence of two different mechanisms for heparin molecules of different sizes to bind langerin depending on their length.
Lead researcher Dr Jesus Angulo from UEA’s school of Pharmacy said: “The molecular recognition of highly charged molecules, like heparin, is a very interesting feature of this important receptor of pathogens. Heparin belongs to the family of glycosaminoglycans, and important family of highly negatively charged polysaccharides abundant in the surface of most of the cells in the form of heparan sulphate, attached to protein cores (proteoglycans). Although still a matter of debate, these interactions are thought to be important in the formation of the granules responsible for internalization and final degradation of HIV-1 particles. In this sense, the structural details provided in this work are of fundamental importance for understanding the mechanisms for ligand recognition developed by Langerhans cells through the langerin receptor, and its potential implications in the process of HIV-1 degradation by this natural barrier”.