uv-light exposed prion protein fails to form amyloid fibrils紫外线暴露朊蛋白未能形成淀粉样纤维.pdfVIP

UV-Light Exposed Prion Protein Fails to Form Amyloid Fibrils Abhay Kumar Thakur, Ch Mohan Rao* Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, Hyderabad, India Abstract Amyloid fibril formation involves three steps; structural perturbation, nucleation and elongation. We have investigated amyloidogenesis using prion protein as a model system and UV-light as a structural perturbant. We find that UV-exposed prion protein fails to form amyloid fibrils. Interestingly, if provided with pre-formed fibrils as seeds, UV-exposed prion protein formed amyloid fibrils albeit with slightly different morphology. Atomic force microscopy and electron microscopic studies clearly show the formation of fibrils under these conditions. Circular dichroism study shows loss in helicity in UV- exposed protein. UV-exposed prion protein fails to form amyloid fibrils. However, it remains competent for fibril extension, suggesting that UV-exposure results in loss of nucleating capability. This work opens up possibility of segregating nucleation and elongation step of amyloidogenesis, facilitating screening of new drug candidates for specifically inhibiting either of these processes. In addition, the work also highlights the importance of light-induced structural and functional alterations which are important in protein based therapeutics. Citation: Thakur AK, Rao CM (2008) UV-Light Exposed Prion Protein Fails to Form Amyloid Fibrils. PLoS ONE 3(7): e2688. doi:10.1371/journal.pone.0002688 Editor: Sotirios Koutsopoulos, Massachusetts Institute of Technology, United States of America Received March 17, 2008; Accepted June 17, 2008; Published July 16, 2008 Copyright: 2008 Thakur et al. This is an open-access article distributed under the terms of the Creative Commons Attribution