This data was extracted from Medline abstracts and full texts (when available) in an automated manner.
The table below describes different point mutations at a given position and provides links to other documents. The sentence(s) where the point mutations in PRIO_MOUSE at position 128 were found are listed after the table.
The experiment shown in Fig. 7 utilized stably transfected lines of CHO cells , described previously (11 , 26 ) , that express WT , PG14 , P101L , D177N / M128 , or F197S / M128V PrP
By performing labeling of unpermeabilized cells , we found that all the mutant PrPs (PG14 , P101L , D177N / M128 , and F197S / M128V) showed less intense surface fluorescence compared with WT PrP (Fig. 7 , left-hand panels)
The human homologs of the PrP mutations are associated with the following diseases: Creutzfeldt-Jakob disease (PG14) , Gerstmann-Sträussler syndrome (P101L and F197S / M128V) , and fatal familial insomnia (D177N / M128)
The human homologs of the PrP mutations are associated with the following diseases: Creutzfeldt-Jakob disease (PG14) , Gerstmann-Stra¨ussler syndrome (P101L and F197S / M128V) , and fatal familial insomnia (D177N / M128)
Reference #3 (Harris D et al.): M128V
We have observed an ER localisation for four different , disease-associated mutations (PG14 , P101L , D177N / M128 , and F197S / M128V) , in CHO as well as BHK cells , and at both low and high expression levels
------------------------------------------------------------------------ (image) Figure 1 Scheme of the primary structure of mature human PrP(23-231) with the known amino acid replacements related to inherited human prion diseases indicated in different colors: CJD , blue ; GSS , red ; FFI , pink ; human polymorphism Met129Val , gray
The figure was created with MOLMOL (93) ------------------------------------------------------------------------ We have introduced all these eight amino acid exchanges separately into mPrP(121-231) , as well as the Met129Val substitution that corresponds to the polymorphism in human PrP determining the disease phenotype linked to the Asp178Asn mutation (35) , and the replacement Thr190Val that corresponds to a polymorphism at positions 108 and 189 in mouse PrP determining the scrapie incubation time in mice (36)
Lane 1 , molecular mass standards ; 2 , wild-type mPrP(121-231) before induction with IPTG ; 3 , wild-type mPrP(121-231) 18 h after induction (same as for the variants shown in the following lanes) ; 4 , Met129Val ; 5 , Met129 / Asp178Asn ; 6 , Met129Val / Asp178Asn ; 7 , Val180Ile ; 8 , Thr183Ala ; 9 , Thr190Val ; 10 , Phe198Ser ; 11 , Glu200Lys ; 12 , Arg208His ; 13 , Val210Ile ; 14 , Gln217Arg
The exchanges Met129Val and Thr190Val correspond to natural polymorphisms in human and mouse PrP , respectively (see text)
As examples , the spectra of the variants Asp178Asn / Met129Val (associated with FFI ; insoluble in the periplasm of E
Like mPrP(121-231) wild type (37) , the TSE-related variants Val180Ile , Glu200Lys , Arg208His , and Val210Ile as well the polymorphism variants Met129Val and Thr190Val were produced as soluble proteins in the periplasm of E
In contrast , the variants Asp178Asn / Met129 , Asp178Asn / Met129Val , Thr183Ala , Phe198Ser , and Gln217LArg could not be obtained in a soluble form in the periplasm (Figure 3)
Thus , the lack of the soluble mPrP(121-231) variants Asp178Asn / Met129 , Asp178Asn / Met129Val , Thr183Ala , Phe198Ser , and Gln217LArg in the periplasm was due to protein aggregation and not due to proteolytic degradation of the polypeptide chains in vivo
Both polymorphism variants Met129Val and Thr190Val as well as the TSE-related variants Glu200Lys and Val210Ile have the same stability as mPrP(121-231) wild type within experimental error ((image)G(image)fold ~ -29 kJ mol-1 ; Table 1)
The exchange of Asp178 by Asn destabilizes the variants Asp178Asn and Asp178Asn / Met129Val by a similar value (~7-8 kJ mol-1)
The five variants with the lowest stabilities , i.e. , Asp178Asn , Met129Val / Asp178Asn , Thr183Ala , Phe198Ser , and Glu217Arg , are exactly those which accumulated in periplasmic indusion bodies , while all other variants with wild type-like stabilities were obtained as soluble proteins (Figure 3 , Table 1)
The isosteric replacement of aspartate 178 to asparagine in the variants Asp178Asn and Asp178Asn / Met129Val affects a solvent-accessible salt bridge (Arg164-H (image) / O (image)-Asp178) and a hydrogen bond (Tyr128-H (image) / O (image)-Asp178) which connect both (image)-strands with helix 2 (27)
This polymorphism at the solvent-exposed residue 129 in the first (image)-strand of PrP C determines the disease phenotype linked to the Asp178Asn substitution in such a way that the Met129 / Asn178 allele segregates with FFI whereas the Val129 / Asn178 allele segregates with familial CJD (35)
The mPrP variants Pro102Leu , Asp178Asn / Met129 , Thr183Ala , and Glu200Lys (numbering according to human PrP) and a protein with an insertion of six additional octapeptide repeats displayed a number of biochemical hallmarks characteristic of PrP Sc such as detergent insolubility , protease resistance , aberrant membrane attachment , and hydrophobicity
In other studies , the expression of human PrP genes harboring the Asp178Asn mutation with Met129 / Val129 (82) and the Gln217Arg mutation (83) in human neuroblastoma cells has been described
We have introduced all these eight amino acid exchanges separately into mPrP(121-231) , as well as the Met129Val substitution that corresponds to the polymorphism in human PrP determining the disease phenotype linked to the Asp178Asn mutation (35) , and the replacement Thr190Val that corresponds to a polymorphism at positions 108 and 189 in mouse PrP determining the scrapie incubation time in mice (36)
We present a complete study on the spectroscopic properties and thermodynamic stabilities of all these mPrP(121-231) variants and compare these findings FIGURE 1: Scheme of the primary structure of mature human PrP(23-231) with the known amino acid replacements related to inherited human prion diseases indicated in different colors: CJD , blue ; GSS , red ; FFI , pink ; human polymorphism Met129Val , gray
Both polymorphism variants Met129Val and Thr190Val as well as the TSE-related variants Glu200Lys and Val210Ile have the same stability as mPrP(121-231) wild type within experimental error ( G°fold -29 kJ mol-1 ; Table 1)
The isosteric replacement of aspartate 178 to asparagine in the variants Asp178Asn and Asp178Asn / Met129Val affects a solvent-accessible salt bridge (Arg164H / O-Asp178) and a hydrogen bond (Tyr128-H / OAsp178) which connect both -strands with helix 2 (27)
This polymorphism at the solvent-exposed residue 129 in the first -strand of PrPC determines the disease phenotype linked to the Asp178Asn substitution in such a way that the Met129 / Asn178 allele segregates with FFI whereas the Val129 / Asn178 allele segregates with familial CJD (35)
Reference #1 (Liemann S et al.): Met129Val
------------------------------------------------------------------------ (image) Figure 1 Scheme of the primary structure of mature human PrP(23-231) with the known amino acid replacements related to inherited human prion diseases indicated in different colors: CJD , blue ; GSS , red ; FFI , pink ; human polymorphism Met129Val , gray
The figure was created with MOLMOL (93) ------------------------------------------------------------------------ We have introduced all these eight amino acid exchanges separately into mPrP(121-231) , as well as the Met129Val substitution that corresponds to the polymorphism in human PrP determining the disease phenotype linked to the Asp178Asn mutation (35) , and the replacement Thr190Val that corresponds to a polymorphism at positions 108 and 189 in mouse PrP determining the scrapie incubation time in mice (36)
Lane 1 , molecular mass standards ; 2 , wild-type mPrP(121-231) before induction with IPTG ; 3 , wild-type mPrP(121-231) 18 h after induction (same as for the variants shown in the following lanes) ; 4 , Met129Val ; 5 , Met129 / Asp178Asn ; 6 , Met129Val / Asp178Asn ; 7 , Val180Ile ; 8 , Thr183Ala ; 9 , Thr190Val ; 10 , Phe198Ser ; 11 , Glu200Lys ; 12 , Arg208His ; 13 , Val210Ile ; 14 , Gln217Arg
The exchanges Met129Val and Thr190Val correspond to natural polymorphisms in human and mouse PrP , respectively (see text)
As examples , the spectra of the variants Asp178Asn / Met129Val (associated with FFI ; insoluble in the periplasm of E
Like mPrP(121-231) wild type (37) , the TSE-related variants Val180Ile , Glu200Lys , Arg208His , and Val210Ile as well the polymorphism variants Met129Val and Thr190Val were produced as soluble proteins in the periplasm of E
In contrast , the variants Asp178Asn / Met129 , Asp178Asn / Met129Val , Thr183Ala , Phe198Ser , and Gln217LArg could not be obtained in a soluble form in the periplasm (Figure 3)
Thus , the lack of the soluble mPrP(121-231) variants Asp178Asn / Met129 , Asp178Asn / Met129Val , Thr183Ala , Phe198Ser , and Gln217LArg in the periplasm was due to protein aggregation and not due to proteolytic degradation of the polypeptide chains in vivo
Both polymorphism variants Met129Val and Thr190Val as well as the TSE-related variants Glu200Lys and Val210Ile have the same stability as mPrP(121-231) wild type within experimental error ((image)G(image)fold ~ -29 kJ mol-1 ; Table 1)
The exchange of Asp178 by Asn destabilizes the variants Asp178Asn and Asp178Asn / Met129Val by a similar value (~7-8 kJ mol-1)
The five variants with the lowest stabilities , i.e. , Asp178Asn , Met129Val / Asp178Asn , Thr183Ala , Phe198Ser , and Glu217Arg , are exactly those which accumulated in periplasmic indusion bodies , while all other variants with wild type-like stabilities were obtained as soluble proteins (Figure 3 , Table 1)
The isosteric replacement of aspartate 178 to asparagine in the variants Asp178Asn and Asp178Asn / Met129Val affects a solvent-accessible salt bridge (Arg164-H (image) / O (image)-Asp178) and a hydrogen bond (Tyr128-H (image) / O (image)-Asp178) which connect both (image)-strands with helix 2 (27)
We have introduced all these eight amino acid exchanges separately into mPrP(121-231) , as well as the Met129Val substitution that corresponds to the polymorphism in human PrP determining the disease phenotype linked to the Asp178Asn mutation (35) , and the replacement Thr190Val that corresponds to a polymorphism at positions 108 and 189 in mouse PrP determining the scrapie incubation time in mice (36)
We present a complete study on the spectroscopic properties and thermodynamic stabilities of all these mPrP(121-231) variants and compare these findings FIGURE 1: Scheme of the primary structure of mature human PrP(23-231) with the known amino acid replacements related to inherited human prion diseases indicated in different colors: CJD , blue ; GSS , red ; FFI , pink ; human polymorphism Met129Val , gray
Both polymorphism variants Met129Val and Thr190Val as well as the TSE-related variants Glu200Lys and Val210Ile have the same stability as mPrP(121-231) wild type within experimental error ( G°fold -29 kJ mol-1 ; Table 1)
The isosteric replacement of aspartate 178 to asparagine in the variants Asp178Asn and Asp178Asn / Met129Val affects a solvent-accessible salt bridge (Arg164H / O-Asp178) and a hydrogen bond (Tyr128-H / OAsp178) which connect both -strands with helix 2 (27)
2005, PrionDB.
cmbi.ru.nl), 22-Aug-2005