Distinct properties of wild-type and the amyloidogenic human cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type
Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy, leading to stroke. Wild-type and variant cystatin C are cysteine proteinase inhibitors which form concentration dependent inactive dimers; howe...
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E-Artikel |
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Oxford, UK: Blackwell Science Ltd ; 2001 |
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Online-Ressource |
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2001 ; Blackwell Publishing Journal Backfiles 1879-2005 |
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In: Journal of neurochemistry - Oxford : Wiley-Blackwell, 1956, 77(2001), 2, Seite 0 |
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volume:77 ; year:2001 ; number:2 ; pages:0 |
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| DOI / URN: |
10.1046/j.1471-4159.2001.00256.x |
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| 520 | |a Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy, leading to stroke. Wild-type and variant cystatin C are cysteine proteinase inhibitors which form concentration dependent inactive dimers; however, variant cystatin C dimerizes at lower concentrations and has an increased susceptibility to a serine protease. We studied the effect of the L68Q amino acid substitution on cystatin C properties, utilizing full length cystatin C purified in mild conditions from media of cells stably transfected with either the wild-type or variant cystatin C genes. The variant cystatin C forms fibrils in vitro detectable by electron microscopy in conditions in which the wild-type protein forms amorphous aggregates. We also show by circular dichroism, steady-state fluorescence and Fourier-transformed infrared spectroscopy that the amino acid substitution modifies cystatin C structure by destabilizing α-helical structures and exposing the tryptophan residue to a more polar environment, yielding a more unfolded molecule. These spectral changes demonstrate that variant cystatin C has a three-dimensional structure different from that of the wild-type protein. The structural differences between variant and wild-type cystatin C account for the susceptibility of the variant protein to unfolding, proteolysis and fibrillogenesis. | ||
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| 700 | 1 | |a Calero, Miguel |4 oth | |
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| 700 | 1 | |a Castaño, Eduardo M. |4 oth | |
| 700 | 1 | |a Sigurdsson, Einar M. |4 oth | |
| 700 | 1 | |a Kumar, Asok |4 oth | |
| 700 | 1 | |a Gallo, Gloria |4 oth | |
| 700 | 1 | |a Frangione, Blas |4 oth | |
| 700 | 1 | |a Levy, Efrat |4 oth | |
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10.1046/j.1471-4159.2001.00256.x doi (DE-627)NLEJ243143966 DE-627 ger DE-627 rakwb Distinct properties of wild-type and the amyloidogenic human cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type Oxford, UK Blackwell Science Ltd 2001 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy, leading to stroke. Wild-type and variant cystatin C are cysteine proteinase inhibitors which form concentration dependent inactive dimers; however, variant cystatin C dimerizes at lower concentrations and has an increased susceptibility to a serine protease. We studied the effect of the L68Q amino acid substitution on cystatin C properties, utilizing full length cystatin C purified in mild conditions from media of cells stably transfected with either the wild-type or variant cystatin C genes. The variant cystatin C forms fibrils in vitro detectable by electron microscopy in conditions in which the wild-type protein forms amorphous aggregates. We also show by circular dichroism, steady-state fluorescence and Fourier-transformed infrared spectroscopy that the amino acid substitution modifies cystatin C structure by destabilizing α-helical structures and exposing the tryptophan residue to a more polar environment, yielding a more unfolded molecule. These spectral changes demonstrate that variant cystatin C has a three-dimensional structure different from that of the wild-type protein. The structural differences between variant and wild-type cystatin C account for the susceptibility of the variant protein to unfolding, proteolysis and fibrillogenesis. 2001 Blackwell Publishing Journal Backfiles 1879-2005 |2001|||||||||| amyloid fibrils Calero, Miguel oth Pawlik, Monika oth Soto, Claudio oth Castaño, Eduardo M. oth Sigurdsson, Einar M. oth Kumar, Asok oth Gallo, Gloria oth Frangione, Blas oth Levy, Efrat oth In Journal of neurochemistry Oxford : Wiley-Blackwell, 1956 77(2001), 2, Seite 0 Online-Ressource (DE-627)NLEJ243927584 (DE-600)2020528-4 1471-4159 nnns volume:77 year:2001 number:2 pages:0 http://dx.doi.org/10.1046/j.1471-4159.2001.00256.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 77 2001 2 0 |
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10.1046/j.1471-4159.2001.00256.x doi (DE-627)NLEJ243143966 DE-627 ger DE-627 rakwb Distinct properties of wild-type and the amyloidogenic human cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type Oxford, UK Blackwell Science Ltd 2001 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy, leading to stroke. Wild-type and variant cystatin C are cysteine proteinase inhibitors which form concentration dependent inactive dimers; however, variant cystatin C dimerizes at lower concentrations and has an increased susceptibility to a serine protease. We studied the effect of the L68Q amino acid substitution on cystatin C properties, utilizing full length cystatin C purified in mild conditions from media of cells stably transfected with either the wild-type or variant cystatin C genes. The variant cystatin C forms fibrils in vitro detectable by electron microscopy in conditions in which the wild-type protein forms amorphous aggregates. We also show by circular dichroism, steady-state fluorescence and Fourier-transformed infrared spectroscopy that the amino acid substitution modifies cystatin C structure by destabilizing α-helical structures and exposing the tryptophan residue to a more polar environment, yielding a more unfolded molecule. These spectral changes demonstrate that variant cystatin C has a three-dimensional structure different from that of the wild-type protein. The structural differences between variant and wild-type cystatin C account for the susceptibility of the variant protein to unfolding, proteolysis and fibrillogenesis. 2001 Blackwell Publishing Journal Backfiles 1879-2005 |2001|||||||||| amyloid fibrils Calero, Miguel oth Pawlik, Monika oth Soto, Claudio oth Castaño, Eduardo M. oth Sigurdsson, Einar M. oth Kumar, Asok oth Gallo, Gloria oth Frangione, Blas oth Levy, Efrat oth In Journal of neurochemistry Oxford : Wiley-Blackwell, 1956 77(2001), 2, Seite 0 Online-Ressource (DE-627)NLEJ243927584 (DE-600)2020528-4 1471-4159 nnns volume:77 year:2001 number:2 pages:0 http://dx.doi.org/10.1046/j.1471-4159.2001.00256.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 77 2001 2 0 |
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10.1046/j.1471-4159.2001.00256.x doi (DE-627)NLEJ243143966 DE-627 ger DE-627 rakwb Distinct properties of wild-type and the amyloidogenic human cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type Oxford, UK Blackwell Science Ltd 2001 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy, leading to stroke. Wild-type and variant cystatin C are cysteine proteinase inhibitors which form concentration dependent inactive dimers; however, variant cystatin C dimerizes at lower concentrations and has an increased susceptibility to a serine protease. We studied the effect of the L68Q amino acid substitution on cystatin C properties, utilizing full length cystatin C purified in mild conditions from media of cells stably transfected with either the wild-type or variant cystatin C genes. The variant cystatin C forms fibrils in vitro detectable by electron microscopy in conditions in which the wild-type protein forms amorphous aggregates. We also show by circular dichroism, steady-state fluorescence and Fourier-transformed infrared spectroscopy that the amino acid substitution modifies cystatin C structure by destabilizing α-helical structures and exposing the tryptophan residue to a more polar environment, yielding a more unfolded molecule. These spectral changes demonstrate that variant cystatin C has a three-dimensional structure different from that of the wild-type protein. The structural differences between variant and wild-type cystatin C account for the susceptibility of the variant protein to unfolding, proteolysis and fibrillogenesis. 2001 Blackwell Publishing Journal Backfiles 1879-2005 |2001|||||||||| amyloid fibrils Calero, Miguel oth Pawlik, Monika oth Soto, Claudio oth Castaño, Eduardo M. oth Sigurdsson, Einar M. oth Kumar, Asok oth Gallo, Gloria oth Frangione, Blas oth Levy, Efrat oth In Journal of neurochemistry Oxford : Wiley-Blackwell, 1956 77(2001), 2, Seite 0 Online-Ressource (DE-627)NLEJ243927584 (DE-600)2020528-4 1471-4159 nnns volume:77 year:2001 number:2 pages:0 http://dx.doi.org/10.1046/j.1471-4159.2001.00256.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 77 2001 2 0 |
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10.1046/j.1471-4159.2001.00256.x doi (DE-627)NLEJ243143966 DE-627 ger DE-627 rakwb Distinct properties of wild-type and the amyloidogenic human cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type Oxford, UK Blackwell Science Ltd 2001 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy, leading to stroke. Wild-type and variant cystatin C are cysteine proteinase inhibitors which form concentration dependent inactive dimers; however, variant cystatin C dimerizes at lower concentrations and has an increased susceptibility to a serine protease. We studied the effect of the L68Q amino acid substitution on cystatin C properties, utilizing full length cystatin C purified in mild conditions from media of cells stably transfected with either the wild-type or variant cystatin C genes. The variant cystatin C forms fibrils in vitro detectable by electron microscopy in conditions in which the wild-type protein forms amorphous aggregates. We also show by circular dichroism, steady-state fluorescence and Fourier-transformed infrared spectroscopy that the amino acid substitution modifies cystatin C structure by destabilizing α-helical structures and exposing the tryptophan residue to a more polar environment, yielding a more unfolded molecule. These spectral changes demonstrate that variant cystatin C has a three-dimensional structure different from that of the wild-type protein. The structural differences between variant and wild-type cystatin C account for the susceptibility of the variant protein to unfolding, proteolysis and fibrillogenesis. 2001 Blackwell Publishing Journal Backfiles 1879-2005 |2001|||||||||| amyloid fibrils Calero, Miguel oth Pawlik, Monika oth Soto, Claudio oth Castaño, Eduardo M. oth Sigurdsson, Einar M. oth Kumar, Asok oth Gallo, Gloria oth Frangione, Blas oth Levy, Efrat oth In Journal of neurochemistry Oxford : Wiley-Blackwell, 1956 77(2001), 2, Seite 0 Online-Ressource (DE-627)NLEJ243927584 (DE-600)2020528-4 1471-4159 nnns volume:77 year:2001 number:2 pages:0 http://dx.doi.org/10.1046/j.1471-4159.2001.00256.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 77 2001 2 0 |
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10.1046/j.1471-4159.2001.00256.x doi (DE-627)NLEJ243143966 DE-627 ger DE-627 rakwb Distinct properties of wild-type and the amyloidogenic human cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type Oxford, UK Blackwell Science Ltd 2001 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy, leading to stroke. Wild-type and variant cystatin C are cysteine proteinase inhibitors which form concentration dependent inactive dimers; however, variant cystatin C dimerizes at lower concentrations and has an increased susceptibility to a serine protease. We studied the effect of the L68Q amino acid substitution on cystatin C properties, utilizing full length cystatin C purified in mild conditions from media of cells stably transfected with either the wild-type or variant cystatin C genes. The variant cystatin C forms fibrils in vitro detectable by electron microscopy in conditions in which the wild-type protein forms amorphous aggregates. We also show by circular dichroism, steady-state fluorescence and Fourier-transformed infrared spectroscopy that the amino acid substitution modifies cystatin C structure by destabilizing α-helical structures and exposing the tryptophan residue to a more polar environment, yielding a more unfolded molecule. These spectral changes demonstrate that variant cystatin C has a three-dimensional structure different from that of the wild-type protein. The structural differences between variant and wild-type cystatin C account for the susceptibility of the variant protein to unfolding, proteolysis and fibrillogenesis. 2001 Blackwell Publishing Journal Backfiles 1879-2005 |2001|||||||||| amyloid fibrils Calero, Miguel oth Pawlik, Monika oth Soto, Claudio oth Castaño, Eduardo M. oth Sigurdsson, Einar M. oth Kumar, Asok oth Gallo, Gloria oth Frangione, Blas oth Levy, Efrat oth In Journal of neurochemistry Oxford : Wiley-Blackwell, 1956 77(2001), 2, Seite 0 Online-Ressource (DE-627)NLEJ243927584 (DE-600)2020528-4 1471-4159 nnns volume:77 year:2001 number:2 pages:0 http://dx.doi.org/10.1046/j.1471-4159.2001.00256.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 77 2001 2 0 |
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Distinct properties of wild-type and the amyloidogenic human cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type |
| abstract |
Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy, leading to stroke. Wild-type and variant cystatin C are cysteine proteinase inhibitors which form concentration dependent inactive dimers; however, variant cystatin C dimerizes at lower concentrations and has an increased susceptibility to a serine protease. We studied the effect of the L68Q amino acid substitution on cystatin C properties, utilizing full length cystatin C purified in mild conditions from media of cells stably transfected with either the wild-type or variant cystatin C genes. The variant cystatin C forms fibrils in vitro detectable by electron microscopy in conditions in which the wild-type protein forms amorphous aggregates. We also show by circular dichroism, steady-state fluorescence and Fourier-transformed infrared spectroscopy that the amino acid substitution modifies cystatin C structure by destabilizing α-helical structures and exposing the tryptophan residue to a more polar environment, yielding a more unfolded molecule. These spectral changes demonstrate that variant cystatin C has a three-dimensional structure different from that of the wild-type protein. The structural differences between variant and wild-type cystatin C account for the susceptibility of the variant protein to unfolding, proteolysis and fibrillogenesis. |
| abstractGer |
Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy, leading to stroke. Wild-type and variant cystatin C are cysteine proteinase inhibitors which form concentration dependent inactive dimers; however, variant cystatin C dimerizes at lower concentrations and has an increased susceptibility to a serine protease. We studied the effect of the L68Q amino acid substitution on cystatin C properties, utilizing full length cystatin C purified in mild conditions from media of cells stably transfected with either the wild-type or variant cystatin C genes. The variant cystatin C forms fibrils in vitro detectable by electron microscopy in conditions in which the wild-type protein forms amorphous aggregates. We also show by circular dichroism, steady-state fluorescence and Fourier-transformed infrared spectroscopy that the amino acid substitution modifies cystatin C structure by destabilizing α-helical structures and exposing the tryptophan residue to a more polar environment, yielding a more unfolded molecule. These spectral changes demonstrate that variant cystatin C has a three-dimensional structure different from that of the wild-type protein. The structural differences between variant and wild-type cystatin C account for the susceptibility of the variant protein to unfolding, proteolysis and fibrillogenesis. |
| abstract_unstemmed |
Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy, leading to stroke. Wild-type and variant cystatin C are cysteine proteinase inhibitors which form concentration dependent inactive dimers; however, variant cystatin C dimerizes at lower concentrations and has an increased susceptibility to a serine protease. We studied the effect of the L68Q amino acid substitution on cystatin C properties, utilizing full length cystatin C purified in mild conditions from media of cells stably transfected with either the wild-type or variant cystatin C genes. The variant cystatin C forms fibrils in vitro detectable by electron microscopy in conditions in which the wild-type protein forms amorphous aggregates. We also show by circular dichroism, steady-state fluorescence and Fourier-transformed infrared spectroscopy that the amino acid substitution modifies cystatin C structure by destabilizing α-helical structures and exposing the tryptophan residue to a more polar environment, yielding a more unfolded molecule. These spectral changes demonstrate that variant cystatin C has a three-dimensional structure different from that of the wild-type protein. The structural differences between variant and wild-type cystatin C account for the susceptibility of the variant protein to unfolding, proteolysis and fibrillogenesis. |
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Distinct properties of wild-type and the amyloidogenic human cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type |
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Calero, Miguel Pawlik, Monika Soto, Claudio Castaño, Eduardo M. Sigurdsson, Einar M. Kumar, Asok Gallo, Gloria Frangione, Blas Levy, Efrat |
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Calero, Miguel Pawlik, Monika Soto, Claudio Castaño, Eduardo M. Sigurdsson, Einar M. Kumar, Asok Gallo, Gloria Frangione, Blas Levy, Efrat |
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