PrionDB: Extraction of mutation data from the literature

2005, PrionDB.

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 F197S 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 F197S in PRIO_MOUSE

Point mutation:	F197S
Cited point mutation:	F198S,Phe198Ser,Phe198
Domain:	Not determined
General numbering (PrionDB):	-
Protein:	PRIO_MOUSE (Prnp,Prn-p)	Swiss-Prot Cross-reference table Family page
Other point mutations / same protein / same position	Point mutations at position 197 in PRIO_MOUSE
Other point mutations / same protein	List of mutations in PRIO_MOUSE
Family alignments	Mammalian prion proteins Prion proteins (PRP, PRNP)
Other point mutations / same position	Position 198 in Mammalian prion proteins family Position 198 in Prion proteins (PRP, PRNP) family
Reference:	Influence of amino acid substitutions related to inherited human prion diseases on the thermodynamic stability of the cellular prion protein. Liemann S, Glockshuber R Biochemistry 1999 Mar 16;38(11):3258-67.	Medline
Other point mutations / same article	List
Text source	HTML and PDF full texts
Validation status	True positive

Relevant sentences:

Phe198Ser

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
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
The amino acid substitutions Gln217Arg and Phe198Ser destabilize mPrP(121-231) by 10.3 and 8.9 kJ mol-1 , respectively , and the variant Thr183Ala shows the lowest (image)G(image)fold of approximately 10 kJ mol-1 (equivalent to a destabilization of the domain by 19.3 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 amino acid substitutions Gln217Arg and Phe198Ser destabilize mPrP(121-231) by
FIGURE 4: (A) Far-UV CD spectra and (B) near-UV CD spectra at pH 7.0 and 25 °C of mPrP(121-231) wild type (solid line) , mPrP(23-231) wild type (dotted line) , and the mPrP(121-231) variants

F198S

------------------------------------------------------------------------ Table 1: Thermodynamic Stabilities of mPrP(121-231) Variants , mPrP(121-231) Wild Type , and Full-Length mPrP(23-231) Wild Type at pH 7.0 and 25 (image)C mPrP protein prion disease phenotype (image)G(image) fold (kJ mol-1)a (image)(image)G(image) fold (variant - wild type) b cooperativity (kJ mol-1 M-1)a [urea]1 / 2 (M) a mPrP(121-231) wt -29.7 ą 1.0 4.8 ą 0.2 6.2 mPrP(23-231) wt -25.5 ą 1.0 4.2 ą 1.9 4.1 ą 0.2 6.3 M129V polymorphism (human) -28.2 ą 1.0 1.4 ą 2.0 4.5 ą 0.2 6.3 D178N / M129 FFI -22.5 ą 0.7 7.2 ą 1.7 4.7 ą 0.1 4.8 D178N / V129 CJD -21.7 ą 0.9 8.0 ą 1.8 4.5 ą 0.2 4.9 V180I GSS -27.6 ą 0.8 2.1 ą 1.7 4.5 ą 0.1 6.2 T183A CJD -10.4 ą 2.1 19.3 ą 3.1 3.5 ą 0.5 3.0 T190V polymorphism (mouse) -30.3 ą 1.5 -0.7 ą 2.4 4.8 ą 0.2 6.4 F198S GSS -19.4 ą 0.8 10.3 ą 1.7 4.4 ą 0.2 4.5 E200K CJD -29.1 ą 1.5 0.6 ą 2.4 4.9 ą 0.3 5.9 R208H CJD -23.7 ą 1.5 6.0 ą 2.5 4.3 ą 0.3 5.6 V210I CJD -28.6 ą 1.6 1.1 ą 2.6 4.5 ą 0.3 6.3 Q217R GSS -20.8 ą 0.8 8.9 ą 1.7 4.5 ą 0.2 4.7 a The thermodynamic stabilities were measured by urea-induced equilibrium transitions (Figure 5)
Table 1: Thermodynamic Stabilities of mPrP(121-231) Variants , mPrP(121-231) Wild Type , and Full-Length mPrP(23-231) Wild Type at pH 7.0 and 25 °C mPrP protein prion disease phenotype G°fold (kJ mol-1)a G°fold (variant - wild type)b cooperativity (kJ mol-1 M-1)a [urea]1 / 2 (M)a mPrP(121-231) wt - -29.7 ( 1.0 - 4.8 ( 0.2 6.2 mPrP(23-231) wt - -25.5 ( 1.0 4.2 ( 1.9 4.1 ( 0.2 6.3 M129V polymorphism (human) -28.2 ( 1.0 1.4 ( 2.0 4.5 ( 0.2 6.3 D178N / M129 FFI -22.5 ( 0.7 7.2 ( 1.7 4.7 ( 0.1 4.8 D178N / V129 CJD -21.7 ( 0.9 8.0 ( 1.8 4.5 ( 0.2 4.9 V180I GSS -27.6 ( 0.8 2.1 ( 1.7 4.5 ( 0.1 6.2 T183A CJD -10.4 ( 2.1 19.3 ( 3.1 3.5 ( 0.5 3.0 T190V polymorphism (mouse) -30.3 ( 1.5 -0.7 ( 2.4 4.8 ( 0.2 6.4 F198S GSS -19.4 ( 0.8 10.3 ( 1.7 4.4 ( 0.2 4.5 E200K CJD -29.1 ( 1.5 0.6 ( 2.4 4.9 ( 0.3 5.9 R208H CJD -23.7 ( 1.5 6.0 ( 2.5 4.3 ( 0.3 5.6 V210I CJD -28.6 ( 1.6 1.1 ( 2.6 4.5 ( 0.3 6.3 Q217R GSS -20.8 ( 0.8 8.9 ( 1.7 4.5 ( 0.2 4.7 a The thermodynamic stabilities were measured by urea-induced equilibrium transitions (Figure 5)

Phe198

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
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
The amino acid substitutions Gln217Arg and Phe198Ser destabilize mPrP(121-231) by 10.3 and 8.9 kJ mol-1 , respectively , and the variant Thr183Ala shows the lowest (image)G(image)fold of approximately 10 kJ mol-1 (equivalent to a destabilization of the domain by 19.3 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 exchange of Phe198 for Ser creates a cavity in the interior of the molecule and lowers the van der Waal's interaction and the buried hydrophobic surface area due to the loss of the phenylalanine , while a polar side chain is introduced into the hydrophobic core
The amino acid substitutions Gln217Arg and Phe198Ser destabilize mPrP(121-231) by
FIGURE 4: (A) Far-UV CD spectra and (B) near-UV CD spectra at pH 7.0 and 25 °C of mPrP(121-231) wild type (solid line) , mPrP(23-231) wild type (dotted line) , and the mPrP(121-231) variants

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