The role of lipid-protein interactions in amyloid-type protein fibril formation.
Structural transition of polypeptide chains into the beta-sheet state followed by amyloid fibril formation is the key characteristic of a number of the so-called conformational diseases. The multistep process of protein fibrillization can be modulated by a variety of factors, in particular by lipid-protein interactions. A wealth of experimental evidence provides support to the notion that amyloid fibril assembly and the toxicity of pre-fibrillar aggregates are closely related and are both intimately membrane associated phenomena. The present review summarizes the principal factors responsible for the enhancement of fibril formation in a membrane environment, viz. (i) structural transformation of polypeptide chain into a partially folded conformation, (ii) increase of the local concentration of a protein upon its membrane binding, (iii) aggregation-favoring orientation of the bound protein, and (iv) variation in the depth of bilayer penetration affecting the nucleation propensity of the membrane associated protein. The molecular mechanisms of membrane-mediated protein fibrillization are discussed. Importantly, the toxicity of lipid-induced pre-fibrillar aggregates is likely to have presented a very strong negative selection pressure in the evolution of amino acid sequences.
Department of Biological and Medical Physics, VN Karazin Kharkiv National University, Ukraine.
Galyna P
GP
Gorbenko
Paavo K J
PK
Kinnunen
D000595:Amino Acid Sequence / Q000502:physiology; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D000682:Amyloid; D008051:Lipid Bilayers; D008055:Lipids