TAILIEUCHUNG - Báo cáo khoa học: Full-length prion protein aggregates to amyloid fibrils and spherical particles by distinct pathways

As limited structural information is available on prion protein (PrP) mis-folding and aggregation, a causative link between the specific (supra)mole-cular structure of PrP and transmissible spongiform encephalopathies remains to be elucidated. | ỊFEBS Journal Full-length prion protein aggregates to amyloid fibrils and spherical particles by distinct pathways Driss El Moustaine1 2 3 Veronique Perrier1 2 3 Laszlo Smeller4 Reinhard Lange1 2 3 and Joan Torrent1 2 3 1 UMR-S710 unit Departement Biologie-Sante Universite Montpellier 2 France 2 Unit 710 Institut Nationalde la Sante et de la Recherche Medicale Montpellier France 3 Laboratoire du vieillisement cérébralet des maladies neurodégénératives Ecole Pratique des Hautes Etudes Paris France 4 Department of Biophysics and Radiation Biology Semmelweis University Budapest Hungary Keywords amyloid fibrils conformationaltransition high pressure prion protein protein aggregation Correspondence J. Torrent INSERM U710 CC 105 Universite de Montpellier 2 Place Eugene Bataillon F-34095 Montpellier Cedex 5 France Fax 33 467 14 33 86 Tel 33 467 14 93 47 E-mail torrent@ Received 8 January 2008 revised 21 February 2008 accepted 22 February 2008 doi As limited structural information is available on prion protein PrP misfolding and aggregation a causative link between the specific supra mole-cular structure of PrP and transmissible spongiform encephalopathies remains to be elucidated. In this study high pressure was utilized as an approach to perturb protein structure to characterize different morphological and structural PrP aggregates. It was shown that full-length recombinant PrP undergoes b-sheet aggregation on high-pressure-induced destabilization. By tuning the physicochemical conditions the assembly process evolves through two distinct pathways leading to the irreversible formation of spherical particles or amyloid fibrils respectively. When the PrP aggregation propensity is enhanced high pressure induces the formation of a partially unfolded aggregated protein AggHP which relaxes at ambient pressure to form amorphous aggregates. The latter largely retain the native secondary structure. On prolonged incubation at high .

TÀI LIỆU LIÊN QUAN
Đã phát hiện trình chặn quảng cáo AdBlock
Trang web này phụ thuộc vào doanh thu từ số lần hiển thị quảng cáo để tồn tại. Vui lòng tắt trình chặn quảng cáo của bạn hoặc tạm dừng tính năng chặn quảng cáo cho trang web này.