Journal
CHEMISTRY AND PHYSICS OF LIPIDS
Volume 141, Issue 1-2, Pages 72-82Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.chemphyslip.2006.02.006
Keywords
protein-lipid interactions; membrane-induced protein aggregation; amyloid fibrils
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Structural transition of polypeptide chains into the P-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. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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