Functional Protein Fibrils in Infectious and Aggregation Diseases

Orateur : Meytal LANDAU (Technion, Israel Institute of Technology, Haifa, Israel)

Protein fibrils that perform physiological activities, such as functional amyloids, could provide new therapeutic venues, mostly due to their roles as key virulence determinants in microbes, antimicrobial activities, and possible involvement in systemic and neurodegenerative diseases. Yet, these fibrous proteins present great challenges in structural and functional studies due to their aggregative and partially disordered nature, and structural polymorphisms observed in similar and even identical sequences. We recently determined the first high resolution structures of bacterial amyloids involved in cytotoxicity and in biofilm structuring (Tayeb-Fligelman et. al., Science 2017 and Salinas et. al., Nat Commun 2018). The structures revealed both similarities and unexpected departures from the structures of pathological human amyloids. This structural insight implies on possible inter-species interactions that could have bearing on amyloid diseases by the creation of transmissible agents. Furthermore, in yet unpublished work, we provided atomic-resolution insight into three fibril-forming antimicrobial peptides, which featured unique morphologies, including a novel type of protein fibril composed of four-helical bundles that spiral into a hexameric configuration, forming sub-nano channels along the fibril. We expect that a detailed molecular understanding on functional fibrils will provide the foundation for translational research and for elucidation of the etiology of and interactions between microbial and human ‘amylomes’ in health and disease.

Télécharger dans mon agenda