Prion protein: Difference between revisions

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Kurt Giles, Jaime Prilusky, Eran Hodis, Claudio Garutti, Michal Harel, Joel L. Sussman

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-The prion protein (PrP) is a cell surface glycoprotein. The cellular isoform (PrP<sup>C</sup>) is predominantly α-helical, but can undergo a structural conversion to a β-sheet rich conformation, termed PrP<sup>Sc</sup>. Prion diseases such as Creutzfeldt Jakob disease (CJD) in people, and bovine spongiform encephalopathy (BSE) commonly known as "mad cow" disease, are characterterized by aggregates of PrP<sup>Sc</sup>, which arise from autocatalytic refolding of PrP<sup>C</sup> in a template-dependent manner.
+The prion protein (PrP) is a cell surface glycoprotein. The cellular isoform (PrP<sup>C</sup>) has two dominas: an dN-terminal region that is natively unstructured, and a C-terminal region from residues ~120-230, which is predominantly α-helical. PrP<sup>C</sup> can undergo a structural conversion to a β-sheet rich conformation, termed PrP<sup>Sc</sup>. Prion diseases such as Creutzfeldt Jakob disease (CJD) in people, and bovine spongiform encephalopathy (BSE) commonly known as "mad cow" disease, are characterterized by aggregates of PrP<sup>Sc</sup>, which arise from autocatalytic refolding of PrP<sup>C</sup> in a template-dependent manner.
 Structure from  a
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-==PrP structures==
+==Selected PrP structures==
-AG2 Mouse PrP 121-231 determined by NMR
+=Human PrP=
-B10 Syrian hamster PrP 90-231 NMR ensemble of 25 structures
+* 1QLX HuPrP                23-230 Average            125-228
-DWY BoPrP               121-230 Average            124-227
+* 1QM0 HuPrP                90-230 Average            125-228
-DWZ BoPrP               121-230 20 structures      124-227
+* 1QM2 HuPrP               121-230 Average            125-228
-DX0 BoPrP                23-230 Average            124-227
+* 1I4M HuPrP               119-226 (X-ray)            119-226
-DX1 BoPrP                23-230 20 structures      124-227
+* 1E1J HuPrP,M166V         125-228 Average            125-228
-E1G HuPrP,M166V         125-228 20 structures      125-228
+* 1E1S HuPrP,S170N         125-228 Average            125-228
-E1J HuPrP,M166V         125-228 Average            125-228
+* 1E1W HuPrP,R220K         125-228 Average            125-228
-E1P HuPrP,S170N         125-228 20 structures      125-228
+* 1FKC HuPrP,E200K          90-231 Average            125-231
-E1S HuPrP,S170N         125-228 Average            125-228
+* 1H0L HuPrP,M166C,E221C   121-230 20 structures      119-230
-E1U HuPrP,R220K         125-228 20 structures      125-228
-E1W HuPrP,R220K         125-228 Average            125-228
+=Other PrPs=
-FKC HuPrP,E200K          90-231 Average            125-231
+=Rodent PrP=
-FO7 HuPrP,E200K          90-231 30 structures      125-231
+* XXXX Mouse PrP determined by NMR
-HJM HuPrP                       Average
-HJN HuPrP                       20 structures
+* 1B10 Syrian hamster PrP 90-231 NMR ensemble of 25 structures
-H0L HuPrP,M166C,E221C   121-230 20 structures      119-230
+DWY Cow PrP               121-230 Average            124-227
-I4M HuPrP               119-226 (X-ray)            119-226
+UW3 Sheep PrP
-QLX HuPrP                23-230 Average            125-228
+* XXXX Frog PrP
-QLZ HuPrP                23-230 20 structures      125-228
+* Chicken PrP
-QM0 HuPrP                90-230 Average            125-228
+* Turtle PrP
-QM1 HuPrP                90-230 20 structures      125-228
-QM2 HuPrP               121-230 Average            125-228
-QM3 HuPrP               121-230 20 structures      125-228
-UW3 OvPrP