1e1u
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HUMAN PRION PROTEIN VARIANT R220K
OverviewOverview
The NMR structures of three single-amino acid variants of the C-terminal, domain of the human prion protein, hPrP(121-230), are presented. In, hPrP(M166V) and hPrP(R220K) the substitution is with the corresponding, residue in murine PrP, and in hPrP(S170N) it is with the corresponding, Syrian hamster residue. All three substitutions are in the surface region, of the structure of the cellular form of PrP (PrP(C)) that is formed by, the C-terminal part of helix 3, with residues 218-230, and a loop of, residues 166-172. This molecular region shows high species variability and, has been implicated in specific interactions with a so far not further, characterized "protein X," and it is related to the species barrier for, transmission of prion diseases. As expected, the three variant, hPrP(121-230) structures have the same global architecture as the, previously determined wild-type bovine, human, murine, and Syrian hamster, prion proteins, but with the present study two localized "conformational, markers" could be related with single amino acid exchanges. These are the, length and quality of definition of helix 3, and the NMR-observability of, the residues in the loop 166-172. Poor definition of the C-terminal part, of helix 3 is characteristic for murine PrP and has now been observed also, for hPrP(R220K), and NMR observation of the complete loop 166-172 has so, far been unique for Syrian hamster PrP and is now also documented for, hPrP(S170N).
DiseaseDisease
Known diseases associated with this structure: Creutzfeldt-Jakob disease OMIM:[176640], Gerstmann-Straussler disease OMIM:[176640], Huntington disease-like 1 OMIM:[176640], Insomnia, fatal familial OMIM:[176640], Prion disease with protracted course OMIM:[176640], Retinitis pigmentosa-11 OMIM:[606419]
About this StructureAbout this Structure
1E1U is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
NMR structures of three single-residue variants of the human prion protein., Calzolai L, Lysek DA, Guntert P, von Schroetter C, Riek R, Zahn R, Wuthrich K, Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8340-5. PMID:10900000
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