Study maps nanobody structure, leading to new ways to potentially fight diseases

Researchers at NYU Abu Dhabi used nuclear magnetic resonance to determine the structure and function of Nb23, a nanobody. This could help to better understand how the protein, which is derived only from an antibody type found in camels (i.e. camels and alpacas), can fight diseases such as rheumatoid, lupus, and psoriasis, lymphoma, and breast cancer.A new study published in Molecules by Visiting Professor of Chemistry Gennaro Eposito and his collaborators Mathias Percipalle (NMR laboratory) explains how they used NMR spectroscopy in order to determine the structure and chemical composition of the Nb23 microbody in water.This is a unique method because scientists usually determine the structure of proteins from solid samples using either X-rays or electron microscopy using frozen solutions. Crystals can be difficult to find and proteins are more mobile and flexible in liquid than they are in solid form, particularly for small species.Researchers can use NMR spectroscopy to map the factors that influence nanobody function and recognize changes that occur when the target protein binds to the nanobody. This prevents, for example, Nb23, abnormal protein aggregation that could lead to functional or degenerative diseases.Researchers are excited to examine the potential of nanobodies in relation to monoclonal antibody disease-fighting proteins. These are laboratory-made proteins that mimic an immune system's ability against harmful antigens like viruses. However, they are hard to manage and conserve, and can hardly penetrate solid tissue due to their small size. Nanobodies are, however, ten times smaller than antibodies and offer greater stability, strong binding affinity as well as good solubility and biocompatibility. This makes them a promising therapeutic alternative.Esposito stated that the team is currently studying several nanobodies, in particular Nb23, and Nb24. These nanobodies bind to beta2-microglobulin, a protein which is a critical component of the immune system. They prevent it from becoming fibrillar deposits, such as those associated with degenerative and functional diseases like Alzheimer's or Parkinson's. Understanding the structure of Nb23, and other important nanobodies, is an essential step towards improving our understanding of their ability to bind to target proteins and helping prevent the onset or recurrence of these diseases.