Natural and synthetic prion structure from X-ray fiber diffraction Export

@article{citeulike:5920754, abstract = {10.1073/pnas.0909006106 A conformational isoform of the mammalian prion protein (PrP) is the sole component of the infectious pathogen that causes the prion diseases. We have obtained X-ray fiber diffraction patterns from infectious prions that show cross-\^{I}² diffraction: meridional intensity at 4.8 \~{A}… resolution, indicating the presence of \^{I}² strands running approximately at right angles to the filament axis and characteristic of amyloid structure. Some of the patterns also indicated the presence of a repeating unit along the fiber axis, corresponding to four \^{I}²-strands. We found that recombinant (rec) PrP amyloid differs substantially from highly infectious brain-derived prions, both in structure as demonstrated by the diffraction data, and in heterogeneity as shown by electron microscopy. In addition to the strong 4.8 \~{A}… meridional reflection, the recPrP amyloid diffraction is characterized by strong equatorial intensity at approximately 10.5 \~{A}…, absent from brain-derived prions, and indicating the presence of stacked \^{I}²-sheets. Synthetic prions recovered from transgenic mice inoculated with recPrP amyloid displayed structural characteristics and homogeneity similar to those of naturally occurring prions. The relationship between the structural differences and prion infectivity is uncertain, but might be explained by any of several hypotheses: only a minority of recPrP amyloid possesses a replication-competent conformation, the majority of recPrP amyloid has to undergo a conformational maturation to acquire replication competency, or inhibitory forms of recPrP amyloid interfere with replication during the initial transmission.}, author = {Wille, Holger and Bian, Wen and McDonald, Michele and Kendall, Amy and Colby, David W. and Bloch, Lillian and Ollesch, Julian and Borovinskiy, Alexander L. and Cohen, Fred E. and Prusiner, Stanley B. and Stubbs, Gerald}, citeulike-article-id = {5920754}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0909006106}, citeulike-linkout-1 = {http://www.pnas.org/content/106/40/16990.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/106/40/16990.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19805070}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19805070}, day = {6}, doi = {10.1073/pnas.0909006106}, journal = {Proceedings of the National Academy of Sciences}, keywords = {prion, structure}, month = {October}, number = {40}, pages = {16990--16995}, posted-at = {2009-10-11 09:56:26}, priority = {2}, title = {Natural and synthetic prion structure from X-ray fiber diffraction}, url = {http://dx.doi.org/10.1073/pnas.0909006106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:5920754 L3 - citeulike-article-id:5920754 N2 - 10.1073/pnas.0909006106 A conformational isoform of the mammalian prion protein (PrP) is the sole component of the infectious pathogen that causes the prion diseases. We have obtained X-ray fiber diffraction patterns from infectious prions that show cross-β diffraction: meridional intensity at 4.8 Å resolution, indicating the presence of β strands running approximately at right angles to the filament axis and characteristic of amyloid structure. Some of the patterns also indicated the presence of a repeating unit along the fiber axis, corresponding to four β-strands. We found that recombinant (rec) PrP amyloid differs substantially from highly infectious brain-derived prions, both in structure as demonstrated by the diffraction data, and in heterogeneity as shown by electron microscopy. In addition to the strong 4.8 Å meridional reflection, the recPrP amyloid diffraction is characterized by strong equatorial intensity at approximately 10.5 Å, absent from brain-derived prions, and indicating the presence of stacked β-sheets. Synthetic prions recovered from transgenic mice inoculated with recPrP amyloid displayed structural characteristics and homogeneity similar to those of naturally occurring prions. The relationship between the structural differences and prion infectivity is uncertain, but might be explained by any of several hypotheses: only a minority of recPrP amyloid possesses a replication-competent conformation, the majority of recPrP amyloid has to undergo a conformational maturation to acquire replication competency, or inhibitory forms of recPrP amyloid interfere with replication during the initial transmission. IS - 40 JF - Proceedings of the National Academy of Sciences EP - 16995 TI - Natural and synthetic prion structure from X-ray fiber diffraction VL - 106 SP - 16990 KW - prion KW - structure AU - Wille, Holger AU - Bian, Wen AU - McDonald, Michele AU - Kendall, Amy AU - Colby, David AU - Bloch, Lillian AU - Ollesch, Julian AU - Borovinskiy, Alexander AU - Cohen, Fred AU - Prusiner, Stanley AU - Stubbs, Gerald PY - 2009/10/06/ UR - http://dx.doi.org/10.1073/pnas.0909006106 ER -