Apolipoprotein A-I: the dual face of a protein

Conformational plasticity and flexibility are key structural features of ApoAI in lipid metabolism. Amyloidogenic single point mutations, associated with incurable familial amyloidosis with fibril deposition in peripheral organs, may have a dramatic impact on the structural and functional features of ApoAI. Here, the consistent body of data on ApoAI variants has been reviewed, with the aim of highlighting the hallmarks of the pathology. In accordance with our observations, as well as that of others, we propose a model that accounts for the alteration of the delicate balance between lipid-free/lipid-bound dynamic states which is based on monomer-to-dimer interconversion via domain swapping.