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 R207H 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 R207H in PRIO_MOUSE

Point mutation:	R207H
Cited point mutation:	R208H,Arg208His,Arg208
Domain:	Not determined
General numbering (PrionDB):	-
Protein:	PRIO_MOUSE (Prnp,Prn-p)	Swiss-Prot Cross-reference table Family page
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 208 in Mammalian prion proteins family Position 208 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:

Arg208

The supernatant was treated with 0.57 mM phenylmethylsulfonyl chloride and 0.7 (image)g / mL pepstatin A (final concentrations) , dialyzed against 10 mM MES-NaOH (pH 5.8) [or against 10 mM sodium acetate (pH 5.0) in the case of variant Arg208His] , and applied to a CM52 cellulose column (30 mL ; Whatman)
mPrP(121-231) was eluted with a linear gradient (800 mL) from 0 to 400 mM NaCl in 10 mM MES-NaOH (pH 5.8) [or 10 mM sodium acetate (pH 5.0) in the case of variant Arg208His]
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
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
The amino acid exchange Val180Ile slightly destabilizes the protein by 2 kJ mol-1 , whereas the Arg208His replacement lowers the stability by 6 kJ mol-1
The exchange of the solvent-exposed Arg208 for His in helix 3 is probably destabilizing due to the low (image)-helix propensity of histidine , since its aromatic (image)-substitution lowers the side chain entropy upon helix formation (60-62)
The supernatant was treated with 0.57 mM phenylmethylsulfonyl chloride and 0.7 ľg / mL pepstatin A (final concentrations) , dialyzed against 10 mM MES-NaOH (pH 5.8) [or against 10 mM sodium acetate (pH 5.0) in the case of variant Arg208His] , and applied to a CM52 cellulose column (30 mL ; Whatman)
The exchange of the solventexposed Arg208 for His in helix -->is probably destabilizing due to the low R-helix propensity of histidine , since its aromatic -substitution lowers the side chain entropy upon helix formation (60-62)

R208H

------------------------------------------------------------------------ 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)

Arg208His

The supernatant was treated with 0.57 mM phenylmethylsulfonyl chloride and 0.7 (image)g / mL pepstatin A (final concentrations) , dialyzed against 10 mM MES-NaOH (pH 5.8) [or against 10 mM sodium acetate (pH 5.0) in the case of variant Arg208His] , and applied to a CM52 cellulose column (30 mL ; Whatman)
mPrP(121-231) was eluted with a linear gradient (800 mL) from 0 to 400 mM NaCl in 10 mM MES-NaOH (pH 5.8) [or 10 mM sodium acetate (pH 5.0) in the case of variant Arg208His]
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
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
The amino acid exchange Val180Ile slightly destabilizes the protein by 2 kJ mol-1 , whereas the Arg208His replacement lowers the stability by 6 kJ mol-1
The supernatant was treated with 0.57 mM phenylmethylsulfonyl chloride and 0.7 ľg / mL pepstatin A (final concentrations) , dialyzed against 10 mM MES-NaOH (pH 5.8) [or against 10 mM sodium acetate (pH 5.0) in the case of variant Arg208His] , and applied to a CM52 cellulose column (30 mL ; Whatman)

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