PrionDB: Extraction of mutation data from the literature

This data was extracted from Medline abstracts and full texts (when available) in an automated manner.

The table below describes the selected point mutation and provides links to other documents. The sentence(s) where the point mutation S170N was found are listed after the table.

The mutated residues are also indicated in the family sequence alignments and hyperlinked to the corresponding mutation pages.

Point mutation S170N in PRIO_HUMAN

Relevant sentences:

S170N

• Based on NMR structure determinations of two mouse PrP variants , mPrP[N174T] and mPrP[S170N , N174T] , this study shows that the structured loop in ePrP C relates to these two local amino acid exchanges , so that mPrP[S170N , N174T] exactly mimics ePrP C

• We then solved the NMR structures of mPrP[N174T] [the variant of recombinant mPrP(121-231) with Asn-174 replaced by Thr] and mPrP[S170N , N174T] [the variant of recombinant mPrP(121-231) with Ser-170 replaced by Asn and Asn-174 replaced by Thr] , and , as a reference , we redetermined the NMR structure of mPrP(121-231) (18 )

• The variant proteins mPrP[S170N , N174T] and mPrP[N174T] were prepared by using the QuikChange site-directed mutagenesis protocol (Stratagene)

• The protein samples used were uniformly 15N-labeled ePrP(23-231) , 15N-labeled and 13C , 15N-labeled ePrP(121-231) , mPrP(121-231) , mPrP[N174T](121-231) and mPrP[S170N , N174T](121-231)

• (B) Same as A for mPrP[S170N , N174T] , with the residues 166-175 in blue

• NMR Structure Determination of mPrP(121-231) , mPrP[N174T] , and mPrP[S170N , N174T]

• The protein mPrP[S170N , N174T] exhibits the same precise definition of the loop 166-175 as was seen in ePrP(121-231) (Fig. 2 A and B ) , and the numbers of observable NOE distance constraints involving the loop segment were comparable for both proteins

• There is also a long-range effect of the amino acid replacements in mPrP[S170N , N174T] in that the helix alpha 3 is well defined over its entire length up to residue 226

• Hydrogen Bonding Polymorphism in the Loop 166-175 of mPrP[S170N , N174T]

• The first part of the loop in mPrP[S170N , N174T] forms a 310-helical turn comprising residues 165-169

• Local hydrogen-bonding polymorphisms in the loop comprising residues 165-175 in mPrP[S170N , N174T]

• Through studies of the variant protein mPrP[S170N , N174T] , where the loop amino acid sequence of ePrP is introduced into mPrP , we then showed that the structured loop of ePrP can be related entirely to this localized exchange of two amino acids

• Experiments with transgenic mice expressing mPrP[S170N , N174T] would now appear to be a promising animal model for such investigations

• Asn-170 alone , as it occurs in Syrian hamster PrP (shPrP) (Fig. 1B ) , partially stabilizes the loop structure , and all backbone amide resonances of the loop have been observed in shPrP (21 , 37 , 38 ) as well as in a designed variant of human PrP , hPrP[S170N] (44 )

• In contrast , introduction of Thr in position 174 of mPrP has no noticeable effects on either structure or NMR spectra of mPrP , and only mPrP[S170N , N174T] shows properties identical to ePrP in the loop region (Fig. 4 )

• Finally , there is also a so-far unexplained long-range effect from this two-amino acid substitution , in that the helix alpha 3 is significantly better defined in mPrP[S170N , N174T] than in wild-type mPrP (18 , 39 )

• Polypeptide segment 165-172 in the energy-minimized NMR structures of bPrP , hPrP , mPrP , shPrP , and ePrP and in mPrP[N174T] and mPrP[S170N , N174T]

• Data deposition: The coordinates of ensembles of the 20 conformers have been deposited in the Protein Data Bank , www.pdb.org {PDB ID codes 1XYW [PDB] [ePrP(121-231)] , 1XYX [mPrP(121-231)] , 1Y15 (mPrP[N174T]) , and 1Y16 (mPrP[S170N , N174T])}

Ser-170

• We then solved the NMR structures of mPrP[N174T] [the variant of recombinant mPrP(121-231) with Asn-174 replaced by Thr] and mPrP[S170N , N174T] [the variant of recombinant mPrP(121-231) with Ser-170 replaced by Asn and Asn-174 replaced by Thr] , and , as a reference , we redetermined the NMR structure of mPrP(121-231) (18 )

• For mPrP[N174T] , no resonances of the backbone amide groups of Asp-167 , Gln-168 , Tyr-169 , Ser-170 , Asn-171 , and Phe-175 were detected in any of the NMR spectra recorded

F.Horn (priondbcmbi.ru.nl), 22-Aug-2005