Key points are not available for this paper at this time.
Hereditary forms of human prion disease are linked to specific mutations in the PRNP gene. It has been postulated that these mutations may facilitate the pathogenic process by reducing the stability of the prion protein (PrP). To test this hypothesis, we characterized the recombinant variants of human PrP(90–231) containing point mutations corresponding to Gerstmann-Straussler-Scheinker disease (P102L), Creutzfeld-Jakob disease (E200K), and fatal familial insomnia (M129/D178N). The first two of these mutants could be recovered form from the periplasmic space of Escherichia coli in a soluble form, whereas the D178N variant aggregated into inclusion bodies. The secondary structure of the two soluble variants was essentially identical to that of the wild-type protein. The thermodynamic stability of these mutants was assessed by unfolding in guanidine hydrochloride and thermal denaturation. The stability properties of the P102L variant were indistinguishable from those of wild-type PrP, whereas the E200K mutation resulted in a very small destabilization of the protein. These data, together with the predictive analysis of other familial mutations, indicate that some hereditary forms of prion disease cannot be rationalized using the concept of mutation-induced thermodynamic destabilization of the cellular prion protein. Hereditary forms of human prion disease are linked to specific mutations in the PRNP gene. It has been postulated that these mutations may facilitate the pathogenic process by reducing the stability of the prion protein (PrP). To test this hypothesis, we characterized the recombinant variants of human PrP(90–231) containing point mutations corresponding to Gerstmann-Straussler-Scheinker disease (P102L), Creutzfeld-Jakob disease (E200K), and fatal familial insomnia (M129/D178N). The first two of these mutants could be recovered form from the periplasmic space of Escherichia coli in a soluble form, whereas the D178N variant aggregated into inclusion bodies. The secondary structure of the two soluble variants was essentially identical to that of the wild-type protein. The thermodynamic stability of these mutants was assessed by unfolding in guanidine hydrochloride and thermal denaturation. The stability properties of the P102L variant were indistinguishable from those of wild-type PrP, whereas the E200K mutation resulted in a very small destabilization of the protein. These data, together with the predictive analysis of other familial mutations, indicate that some hereditary forms of prion disease cannot be rationalized using the concept of mutation-induced thermodynamic destabilization of the cellular prion protein. prion protein cellular form of prion protein proteinase K-resistant form of prion protein guanidine hydrochloride human prion protein domain 90–231. Prion diseases, also known as spongiform encephalopathies, are disorders of the central nervous system. Originally described in sheep under the name of scrapie, they affect both humans and animals. These diseases are unique in that they may arise sporadically, may be inherited, or may be acquired by transmission of an infectious agent (1Prusiner S.B. DeArmond S.J. Annu. Rev. Neurosci. 1994; 17: 311-339Crossref PubMed Scopus (158) Google Scholar, 2Weissmann C. FEBS Lett. 1996; 389: 3-11Crossref PubMed Scopus (145) Google Scholar, 3Parchi P. Gambetti P. Picardo P. Ghetti B. Haddock G.M. Progress in Pathology IV. Churchill Scholar, S.B. PubMed Scopus Google of the prion a of B. PubMed Scopus Google Scholar, C. 389: PubMed Scopus Google to the PubMed Scopus Google Scholar, S.B. PubMed Scopus Google the in the disease an protein an of a cellular that by a and in The and by a to the protein S.B. PubMed Scopus Google The two protein soluble and by proteinase as an that to proteinase and has the of an S.B. PubMed Scopus Google Scholar, B. P. S.B. C. PubMed Scopus Google These in properties of the two whereas to a of structure S.B. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, 1996; PubMed Scopus Google Scholar, S.B. PubMed Scopus Google Scholar, FEBS Lett. PubMed Scopus Google Scholar, S.B. PubMed Scopus Google The that spongiform may be as disorders of protein and that the in the pathogenic process the the of and the of S.B. PubMed Scopus Google Scholar, Scopus Google Scholar, PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google the of this human spongiform fatal familial and Gerstmann-Straussler-Scheinker these disorders been linked to specific mutations in the PRNP P. Gambetti P. Picardo P. Ghetti B. Haddock G.M. Progress in Pathology IV. Churchill Scholar, S.B. PubMed Scopus Google It has been that these mutations facilitate the of the prion protein by the structure of S.B. PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google the we the stability of the recombinant containing mutations with familial forms of prion that these mutations a the thermodynamic stability of the that hereditary forms of prion disease be rationalized using the concept of mutation-induced thermodynamic destabilization of with the wild-type Gambetti P. PubMed Scopus Google we characterized protein variants with the point and The wild-type and the P102L and E200K mutants were in a soluble form into the periplasmic space of These were to or as by and by and the D178N was a to that of the other aggregated in inclusion and very protein was recovered in a soluble of the P102L and E200K variants were very to those of the wild-type protein are in a of the of the P102L and E200K mutants were essentially indistinguishable from that of the wild-type these mutations in of the protein secondary and of mutations the thermodynamic stability of PrP(90–231) was by unfolding in the unfolding of both the wild-type protein as as the P102L and E200K variants be described as a The thermodynamic from the unfolding are in of these that the P102L mutation the protein thermodynamic of the of the wild-type and E200K PrP(90–231) a small destabilization of the The of in the of the from the of the unfolding to PubMed Scopus Google the of a of may be with by the in to the wild-type the corresponding to the unfolding PubMed Scopus Google The of in of a small in the stability of the E200K of variants in guanidine hydrochloride the wild-type and the E200K The the P102L are essentially identical to those the wild-type protein and are of the to the unfolding of the of two to the of the of and the the of of unfolding the of unfolding to The of the wild-type protein in Gambetti P. PubMed Scopus Google The a of the in the of the wild-type and protein the of the protein PubMed Scopus Google and the and the of the thermal in a The of the of a Gambetti P. PubMed Scopus Google unfolding were the wild-type protein and the P102L and E200K mutants These may be to the Gambetti P. PubMed Scopus Google PubMed Scopus Google to a of and the of an analysis to of small the protein The under corresponding to the of a are from those of the protein These a that the a of a the structure of this properties to be from those of a are characterized by secondary are the of the by the wild-type and the P102L and E200K of variants in the of guanidine hydrochloride wild-type P102L E200K the of hereditary pathogenic mutations the stability of the recombinant prion protein was by thermal denaturation. the the thermal unfolding of both wild-type and was and in protein The the as as the were identical to those the the unfolding and were These with the of thermal PrP(90–231) S.B. PubMed Scopus Google The may be to the protein in the The thermal unfolding the P102L was indistinguishable from that the wild-type the unfolding of E200K of these to a the unfolding and of in these data, we the of of the E200K to of the protein. a of the of destabilization of the to the wild-type protein P. PubMed Scopus Google to both the and thermal indicate an essentially thermodynamic stability of the P102L variant and a in the stability of the E200K of variants wild-type E200K The the P102L was indistinguishable from that the wild-type protein and of the are and the of with indicate that this has a the secondary the the P102L mutation could affect the of the protein. a be in the thermodynamic stability in an the domain S.B. PubMed Scopus Google Scholar, FEBS Lett. PubMed Scopus Google Scholar, S.B. PubMed Scopus Google The of PrP(90–231) in the of may be by the of the to as PubMed Scopus Google The the wild-type protein and the P102L are in The from these are essentially identical both an of to These the that the to in the of the of the of the and P102L variants of the of in the and of the of the protein hypothesis, the central in the of prion diseases the of into an (1Prusiner S.B. DeArmond S.J. Annu. Rev. Neurosci. 1994; 17: 311-339Crossref PubMed Scopus (158) Google Scholar, 2Weissmann C. FEBS Lett. 1996; 389: 3-11Crossref PubMed Scopus (145) Google Scholar, 3Parchi P. Gambetti P. Picardo P. Ghetti B. Haddock G.M. Progress in Pathology IV. Churchill Scholar, S.B. PubMed Scopus Google Scholar, Scopus Google with the recombinant prion protein indicate that characterized by thermodynamic stability Gambetti P. PubMed Scopus Google Scholar, 1996; Scopus Google in the of of a structure be a process destabilization of and of PubMed Scopus Google PubMed Scopus Google Scholar, PubMed Google Scholar, 1996; Scopus Google the transmission of prion disorders and the process in hereditary spongiform to P. Gambetti P. Picardo P. Ghetti B. Haddock G.M. Progress in Pathology IV. Churchill with variants containing familial mutations the of the It has been postulated that the of these mutations to the structure of S.B. PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google a the to that be destabilization of PubMed Scopus Google The of the concept of mutation-induced protein destabilization has been some other diseases PubMed Scopus Google PubMed Google Scholar, PubMed Scopus Google the of familial mutations the structure and thermodynamic stability of the prion protein has to be the of pathogenic mutations the thermodynamic stability of prion we the recombinant the recombinant protein and the secondary and structure to be very to that of from the S.B. PubMed Scopus Google the of the recombinant protein as a of the of the that the thermodynamic mutants has been from in the unfolding and this the stability of into the of mutations the thermodynamic properties of the variants in this to of hereditary human spongiform P. Gambetti P. Picardo P. Ghetti B. Haddock G.M. Progress in Pathology IV. Churchill the first of these mutations has the thermodynamic stability of the E200K to in a very small destabilization of the protein. that a could the with the E200K to the P102L and E200K mutations could be in the unfolding are to the of a Gambetti P. PubMed Scopus Google thermodynamic of the D178N the that in the this cannot be in a soluble form that has may be rationalized with the recombinant 1996; PubMed Scopus Google Scholar, S.B. PubMed Scopus Google Scholar, S.B. PubMed Scopus Google The indicate a the of and the of The D178N mutation this in destabilization of the protein. in to the mutation in this may with the to of the protein. in protein stability may also be a of the other familial be the the a space that be with the small destabilization of structure to be a of mutations with hereditary prion the domain of that that the was the P102L the this may be that other mutations the a the stability of the protein and a small to The very small destabilization the E200K may be by and indicate that the pathogenic mutations a the thermodynamic stability of the human prion and hereditary forms of the disease may be rationalized a the mutation-induced in stability of the other the protein destabilization be to familial mutations affect the of prion protein. It also that some of the mutations may facilitate in prion protein by of with S.B. PubMed Scopus Google Scholar, B. PubMed Scopus Google or cellular 1996; PubMed Scopus Google or by with cellular of the protein. Prion diseases, also known as spongiform encephalopathies, are disorders of the central nervous system. Originally described in sheep under the name of scrapie, they affect both humans and animals. These diseases are unique in that they may arise sporadically, may be inherited, or may be acquired by transmission of an infectious agent (1Prusiner S.B. DeArmond S.J. Annu. Rev. Neurosci. 1994; 17: 311-339Crossref PubMed Scopus (158) Google Scholar, 2Weissmann C. FEBS Lett. 1996; 389: 3-11Crossref PubMed Scopus (145) Google Scholar, 3Parchi P. Gambetti P. Picardo P. Ghetti B. Haddock G.M. Progress in Pathology IV. Churchill Scholar, S.B. PubMed Scopus Google The of the prion a of B. PubMed Scopus Google Scholar, C. 389: PubMed Scopus Google to the PubMed Scopus Google Scholar, S.B. PubMed Scopus Google the in the disease an protein an of a cellular that by a and in The and by a to the protein S.B. PubMed Scopus Google The two protein soluble and by proteinase as an that to proteinase and has the of an S.B. PubMed Scopus Google Scholar, B. P. S.B. C. PubMed Scopus Google These in properties of the two whereas to a of structure S.B. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, 1996; PubMed Scopus Google Scholar, S.B. PubMed Scopus Google Scholar, FEBS Lett. PubMed Scopus Google Scholar, S.B. PubMed Scopus Google The that spongiform may be as disorders of protein and that the in the pathogenic process the the of and the of S.B. PubMed Scopus Google Scholar, Scopus Google Scholar, PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google the of this Hereditary human spongiform fatal familial and Gerstmann-Straussler-Scheinker these disorders been linked to specific mutations in the PRNP P. Gambetti P. Picardo P. Ghetti B. Haddock G.M. Progress in Pathology IV. Churchill Scholar, S.B. PubMed Scopus Google It has been that these mutations facilitate the of the prion protein by the structure of S.B. PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google the we the stability of the recombinant containing mutations with familial forms of prion that these mutations a the thermodynamic stability of the that hereditary forms of prion disease be rationalized using the concept of mutation-induced thermodynamic destabilization of with the wild-type Gambetti P. PubMed Scopus Google we characterized protein variants with the point and The wild-type and the P102L and E200K mutants were in a soluble form into the periplasmic space of These were to or as by and by and the D178N was a to that of the other aggregated in inclusion and very protein was recovered in a soluble of the P102L and E200K variants were very to those of the wild-type protein are in a of the of the P102L and E200K mutants were essentially indistinguishable from that of the wild-type these mutations in of the protein secondary and of mutations the thermodynamic stability of PrP(90–231) was by unfolding in the unfolding of both the wild-type protein as as the P102L and E200K variants be described as a The thermodynamic from the unfolding are in of these that the P102L mutation the protein thermodynamic of the of the wild-type and E200K PrP(90–231) a small destabilization of the The of in the of the from the of the unfolding to PubMed Scopus Google the of a of may be with by the in to the wild-type the corresponding to the unfolding PubMed Scopus Google The of in of a small in the stability of the E200K unfolding of the of two to the of the of and the the of of unfolding the of unfolding to The of the wild-type protein in Gambetti P. PubMed Scopus Google The a of the in the of the wild-type and protein the of the protein PubMed Scopus Google and the and the of the thermal in a The of the of a Gambetti P. PubMed Scopus Google unfolding were the wild-type protein and the P102L and E200K mutants These may be to the Gambetti P. PubMed Scopus Google PubMed Scopus Google to a of and the of an analysis to of small the protein The under corresponding to the of a are from those of the protein These a that the a of a the structure of this properties to be from those of a are characterized by secondary are the of the by the wild-type and the P102L and E200K of variants in the of guanidine hydrochloride wild-type P102L E200K the of hereditary pathogenic mutations the stability of the recombinant prion protein was by thermal denaturation. the the thermal unfolding of both wild-type and was and in protein The the as as the were identical to those the the unfolding and were These with the of thermal PrP(90–231) S.B. PubMed Scopus Google The may be to the protein in the The thermal unfolding the P102L was indistinguishable from that the wild-type the unfolding of E200K of these to a the unfolding and of in these data, we the of of the E200K to of the protein. a of the of destabilization of the to the wild-type protein P. PubMed Scopus Google to both the and thermal indicate an essentially thermodynamic stability of the P102L variant and a in the stability of the E200K of variants wild-type E200K The the P102L was indistinguishable from that the wild-type protein and of the are and the of with indicate that this has a the secondary the the P102L mutation could affect the of the protein. a be in the thermodynamic stability in an the domain S.B. PubMed Scopus Google Scholar, FEBS Lett. PubMed Scopus Google Scholar, S.B. PubMed Scopus Google The of PrP(90–231) in the of may be by the of the to as PubMed Scopus Google The the wild-type protein and the P102L are in The from these are essentially identical both an of to These the that the to in the of the of the of the and P102L variants of the of in the and of with the wild-type Gambetti P. PubMed Scopus Google we characterized protein variants with the point and The wild-type and the P102L and E200K mutants were in a soluble form into the periplasmic space of These were to or as by and by and the D178N was a to that of the other aggregated in inclusion and very protein was recovered in a soluble The of the P102L and E200K variants were very to those of the wild-type protein are in a of the of the P102L and E200K mutants were essentially indistinguishable from that of the wild-type these mutations in of the protein secondary and The of mutations the thermodynamic stability of PrP(90–231) was by unfolding in the unfolding of both the wild-type protein as as the P102L and E200K variants be described as a The thermodynamic from the unfolding are in of these that the P102L mutation the protein thermodynamic of the of the wild-type and E200K PrP(90–231) a small destabilization of the The of in the of the from the of the unfolding to PubMed Scopus Google the of a of may be with by the in to the wild-type the corresponding to the unfolding PubMed Scopus Google The of in of a small in the stability of the E200K The the of two to the of the of and the the of of unfolding the of unfolding to The of the wild-type protein in Gambetti P. PubMed Scopus Google The a of the in the of the wild-type and protein the of the protein PubMed Scopus Google and the and the of the thermal The of the of a Gambetti P. PubMed Scopus Google unfolding were the wild-type protein and the P102L and E200K mutants These may be to the Gambetti P. PubMed Scopus Google PubMed Scopus Google to a of and the of an analysis to of small the protein The under corresponding to the of a are from those of the protein These a that the a of a the structure of this properties to be from those of a are characterized by secondary are the of the by the wild-type and the P102L and E200K The of hereditary pathogenic mutations the stability of the recombinant prion protein was by thermal denaturation. the the thermal unfolding of both wild-type and was and in protein The the as as the were identical to those the the unfolding and were These with the of thermal PrP(90–231) S.B. PubMed Scopus Google The may be to the protein in the The thermal unfolding the P102L was indistinguishable from that the wild-type the unfolding of E200K of these to a the unfolding and of in these data, we the of of the E200K to of the protein. a of the of destabilization of the to the wild-type protein P. PubMed Scopus Google to both the and thermal indicate an essentially thermodynamic stability of the P102L variant and a in the stability of the E200K of with indicate that this has a the secondary the the P102L mutation could affect the of the protein. a be in the thermodynamic stability in an the domain S.B. PubMed Scopus Google Scholar, FEBS Lett. PubMed Scopus Google Scholar, S.B. PubMed Scopus Google The of PrP(90–231) in the of may be by the of the to as PubMed Scopus Google The the wild-type protein and the P102L are in The from these are essentially identical both an of to These the that the to in the of the protein. of with indicate that this has a the secondary the the P102L mutation could affect the of the protein. a be in the thermodynamic stability in an the domain S.B. PubMed Scopus Google Scholar, FEBS Lett. PubMed Scopus Google Scholar, S.B. PubMed Scopus Google The of PrP(90–231) in the of may be by the of the to as PubMed Scopus Google The the wild-type protein and the P102L are in The from these are essentially identical both an of to These the that the to in the of the protein. of with indicate that this has a the secondary the the P102L mutation could affect the of the protein. a be in the thermodynamic stability in an the domain S.B. PubMed Scopus Google Scholar, FEBS Lett. PubMed Scopus Google Scholar, S.B. PubMed Scopus Google The of PrP(90–231) in the of may be by the of the to as PubMed Scopus Google The the wild-type protein and the P102L are in The from these are essentially identical both an of to These the that the to in the of the protein. The of with indicate that this has a the secondary the the P102L mutation could affect the of the protein. a be in the thermodynamic stability in an the domain S.B. PubMed Scopus Google Scholar, FEBS Lett. PubMed Scopus Google Scholar, S.B. PubMed Scopus Google The of PrP(90–231) in the of may be by the of the to as PubMed Scopus Google The the wild-type protein and the P102L are in The from these are essentially identical both an of to These the that the to in the of the protein. the of the protein hypothesis, the central in the of prion diseases the of into an (1Prusiner S.B. DeArmond S.J. Annu. Rev. Neurosci. 1994; 17: 311-339Crossref PubMed Scopus (158) Google Scholar, 2Weissmann C. FEBS Lett. 1996; 389: 3-11Crossref PubMed Scopus (145) Google Scholar, 3Parchi P. Gambetti P. Picardo P. Ghetti B. Haddock G.M. Progress in Pathology IV. Churchill Scholar, S.B. PubMed Scopus Google Scholar, Scopus Google with the recombinant prion protein indicate that characterized by thermodynamic stability Gambetti P. PubMed Scopus Google Scholar, 1996; Scopus Google in the of of a structure be a process destabilization of and of PubMed Scopus Google PubMed Scopus Google Scholar, PubMed Google Scholar, 1996; Scopus Google the transmission of prion disorders and the process in hereditary spongiform to P. Gambetti P. Picardo P. Ghetti B. Haddock G.M. Progress in Pathology IV. Churchill with variants containing familial mutations the of the It has been postulated that the of these mutations to the structure of S.B. PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google a the to that be destabilization of PubMed Scopus Google The of the concept of mutation-induced protein destabilization has been some other diseases PubMed Scopus Google PubMed Google Scholar, PubMed Scopus Google the of familial mutations the structure and thermodynamic stability of the prion protein has to be the of pathogenic mutations the thermodynamic stability of prion we the recombinant the recombinant protein and the secondary and structure to be very to that of from the S.B. PubMed Scopus Google the of the recombinant protein as a of the of the that the thermodynamic mutants has been from in the unfolding and this the stability of into the of mutations the thermodynamic properties of the variants in this to of hereditary human spongiform P. Gambetti P. Picardo P. Ghetti B. Haddock G.M. Progress in Pathology IV. Churchill the first of these mutations has the thermodynamic stability of the E200K to in a very small destabilization of the protein. that a could the with the E200K to the P102L and E200K mutations could be in the unfolding are to the of a Gambetti P. PubMed Scopus Google thermodynamic of the D178N the that in the this cannot be in a soluble form that has may be rationalized with the recombinant 1996; PubMed Scopus Google Scholar, S.B. PubMed Scopus Google Scholar, S.B. PubMed Scopus Google The indicate a the of and the of The D178N mutation this in destabilization of the protein. in to the mutation in this may with the to of the protein. in protein stability may also be a of the other familial be the the a space that be with the small destabilization of structure to be a of mutations with hereditary prion the domain of that that the was the P102L the this may be that other mutations the a the stability of the protein and a small to The very small destabilization the E200K may be by and indicate that the pathogenic mutations a the thermodynamic stability of the human prion and hereditary forms of the disease may be rationalized a the mutation-induced in stability of the other the protein destabilization be to familial mutations affect the of prion protein. It also that some of the mutations may facilitate in prion protein by of with S.B. PubMed Scopus Google Scholar, B. PubMed Scopus Google or cellular 1996; PubMed Scopus Google or by with cellular of the protein. the of the protein hypothesis, the central in the of prion diseases the of into an (1Prusiner S.B. DeArmond S.J. Annu. Rev. Neurosci. 1994; 17: 311-339Crossref PubMed Scopus (158) Google Scholar, 2Weissmann C. FEBS Lett. 1996; 389: 3-11Crossref PubMed Scopus (145) Google Scholar, 3Parchi P. Gambetti P. Picardo P. Ghetti B. Haddock G.M. Progress in Pathology IV. Churchill Scholar, S.B. PubMed Scopus Google Scholar, Scopus Google with the recombinant prion protein indicate that characterized by thermodynamic stability Gambetti P. PubMed Scopus Google Scholar, 1996; Scopus Google in the of of a structure be a process destabilization of and of PubMed Scopus Google PubMed Scopus Google Scholar, PubMed Google Scholar, 1996; Scopus Google the transmission of prion disorders and the process in hereditary spongiform to P. Gambetti P. Picardo P. Ghetti B. Haddock G.M. Progress in Pathology IV. Churchill with variants containing familial mutations the of the It has been postulated that the of these mutations to the structure of S.B. PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google Scholar, S.B. 1994; PubMed Scopus Google a the to that be destabilization of PubMed Scopus Google The of the concept of mutation-induced protein destabilization has been some other diseases PubMed Scopus Google PubMed Google Scholar, PubMed Scopus Google the of familial mutations the structure and thermodynamic stability of the prion protein has to be To the of pathogenic mutations the thermodynamic stability of prion we the recombinant the recombinant protein and the secondary and structure to be very to that of from the S.B. PubMed Scopus Google the of the recombinant protein as a of the of the that the thermodynamic mutants has been from in the unfolding and this the stability of into the of mutations the thermodynamic properties of the The variants in this to of hereditary human spongiform P. Gambetti P. Picardo P. Ghetti B. Haddock G.M. Progress in Pathology IV. Churchill the first of these mutations has the thermodynamic stability of the E200K to in a very small destabilization of the protein. that a could the with the E200K to the P102L and E200K mutations could be in the unfolding are to the of a Gambetti P. PubMed Scopus Google thermodynamic of the D178N the that in the this cannot be in a soluble form that has The may be rationalized with the recombinant 1996; PubMed Scopus Google Scholar, S.B. PubMed Scopus Google Scholar, S.B. PubMed Scopus Google The indicate a the of and the of The D178N mutation this in destabilization of the protein. in to the mutation in this may with the to of the protein. in protein stability may also be a of the other familial be the the a space that be with the small destabilization of structure to be a of mutations with hereditary prion the domain of that that the was the P102L the this may be that other mutations the a the stability of the protein and a small to The very small destabilization the E200K may be by and indicate that the pathogenic mutations a the thermodynamic stability of the human prion and hereditary forms of the disease may be rationalized a the mutation-induced in stability of the other the protein destabilization be to familial mutations affect the of prion protein. It also that some of the mutations may facilitate in prion protein by of with S.B. PubMed Scopus Google Scholar, B. PubMed Scopus Google or cellular 1996; PubMed Scopus Google or by with cellular of the protein. and
Świętnicki et al. (Sun,) studied this question.