The IBS BAG includes in this proposal IBS teams and external groups from CEA-Cadarache (St Paul lez Durance) and IRBA (Brétigny-sur-Orge). We study structure-function relationships of proteins emphasizing in human health, biotechnology and methodology. Most of the projects are a continuation of the MX-2498 proposal and can be grouped into different topics as follows: host-pathogen interaction, new therapy targets, fundamental cellular mechanisms, membrane proteins, biotechnological applications and methodology. Some of these projects use integrative approaches (X-ray crystallography, cryo-EM, SAXS and NMR), together with other biophysical and biochemical studies, and very recently the use of AI, with the aim to fully understand the complexity of the biological macromolecular systems under study.