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Human cystatin C, a...
Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping
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Janowski, Robert (författare)
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Kozak, Maciej (författare)
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Jankowska, Elzbieta (författare)
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Grzonka, Zbigniew (författare)
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- Grubb, Anders (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine
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- Abrahamson, Magnus (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Proteasinhibitorforskning,Forskargrupper vid Lunds universitet,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Protease Inhibitor Research,Lund University Research Groups
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Jaskolski, Mariusz (författare)
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(creator_code:org_t)
- Springer Science and Business Media LLC, 2001
- 2001
- Engelska.
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Ingår i: Nature Structural Biology. - : Springer Science and Business Media LLC. - 1072-8368. ; 8:4, s. 316-320
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http://dx.doi.org/10...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The crystal structure of human cystatin C, a protein with amyloidogenic properties and a potent inhibitor of cysteine proteases, reveals how the protein refolds to produce very tight two-fold symmetric dimers while retaining the secondary structure of the monomeric form. The dimerization occurs through three-dimensional domain swapping, a mechanism for forming oligomeric proteins. The reconstituted monomer-like domains are similar to chicken cystatin except for one inhibitory loop that unfolds to form the open interface of the dimer. The structure explains the tendency of human cystatin C to dimerize and suggests a mechanism for its aggregation in the brain arteries of elderly people with amyloid angiopathy. A more severe conformational disease is associated with the L68Q mutant of human cystatin C, which causes massive amyloidosis, cerebral hemorrhage and death in young adults. The structure of the three-dimensional domain-swapped dimers shows how the L68Q mutation destabilizes the monomers and makes the partially unfolded intermediate less unstable. Higher aggregates may arise through the three-dimensional domain-swapping mechanism occurring in an open-ended fashion in which partially unfolded molecules are linked into infinite chains.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
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- ref (ämneskategori)
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