Sökning: WFRF:(Sieradzan Adam K.)
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Structural characte...
Structural characterization of covalently stabilized human cystatin c oligomers
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- Chrabaszczewska, Magdalena (författare)
- Adam Mickiewicz University in Poznań,University of Warsaw
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- Sieradzan, Adam K. (författare)
- Medical University of Gdansk
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- Rodziewicz-Motowidło, Sylwia (författare)
- Medical University of Gdansk
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- Grubb, Anders (författare)
- Lund University,Lunds universitet,Cystatin C, njursjukdom, amyloidos och antibiotika,Forskargrupper vid Lunds universitet,Cystatin C, renal disease, amyloidosis and antibiotics,Lund University Research Groups,Skåne University Hospital
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- Dobson, Christopher M. (författare)
- University of Cambridge
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- Kumita, Janet R. (författare)
- University of Cambridge
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- Kozak, Maciej (författare)
- Adam Mickiewicz University in Poznań
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(creator_code:org_t)
- 2020-08-15
- 2020
- Engelska 17 s.
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:16
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://www.mdpi.com...
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Human cystatin C (HCC), a cysteine-protease inhibitor, exists as a folded monomer under physiological conditions but has the ability to self-assemble via domain swapping into multimeric states, including oligomers with a doughnut-like structure. The structure of the monomeric HCC has been solved by X-ray crystallography, and a covalently linked version of HCC (stab-1 HCC) is able to form stable oligomeric species containing 10–12 monomeric subunits. We have performed molecular modeling, and in conjunction with experimental parameters obtained from atomic force microscopy (AFM), transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) measurements, we observe that the structures are essentially flat, with a height of about 2 nm, and the distance between the outer edge of the ring and the edge of the central cavity is ~5.1 nm. These dimensions correspond to the height and diameter of one stab-1 HCC subunit and we present a dodecamer model for stabilized cystatin C oligomers using molecular dynamics simulations and experimentally measured parameters. Given that oligomeric species in protein aggregation reactions are often transient and very highly heterogeneous, the structural information presented here on these isolated stab-1 HCC oligomers may be useful to further explore the physiological relevance of different structural species of cystatin C in relation to protein misfolding disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Cystatin C
- Domain swapping
- Oligomers
- Protein misfolding
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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