2019 年 42 巻 6 号 p. 867-872
Dynamic conformational transitions and molecular assemblies are essential properties of proteins, and relevant to their biological and pathological functions. Neurodegenerative diseases are known to be caused by abnormal, toxic assemblies of related proteins, e.g., amyloid β (Aβ) in Alzheimer’s disease. Growing evidence indicates that the aggregation of various amyloidogenic proteins, including Aβ, can be highly enhanced at glycolipid membranes, suggesting that dynamic glycolipid-dependent conformational changes of proteins constitute crucial steps for their subsequent pathogenic amyloid fibril formation. It has also been proposed that several proteins, including molecular chaperones, can capture amyloidogenic proteins and thereby suppress their fibrillization. NMR spectroscopy provides a powerful tool for characterizing the conformational dynamics and intermolecular interactions of proteins, as well as for exploring transiently formed weak interactions among proteins in solution with various biomolecules, such as glycolipids. Our research group therefore attempted to elucidate the structural basis of protein–glycolipid and protein–protein interactions that either promote or suppress molecular assemblies of amyloidogenic proteins, using both solution and solid-state NMR methods in conjunction with other biophysical techniques. Our findings provide structural views of molecular processes involving amyloidogenic proteins of clinical and pathological interest and offer clues for the development of drugs to prevent and treat neurodegenerative diseases.