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The domain swapping of human cystatin C induced by synchrotron radiation

Taube, Michal ; Pietralik, Zuzanna ; Szymanska, Aneta ; Szutkowski, Kosma ; Clemens, Daniel ; Grubb, Anders LU orcid and Kozak, Maciej (2019) In Scientific Reports 9(1).
Abstract

Domain swapping is observed for many proteins with flexible conformations. This phenomenon is often associated with the development of conformational diseases. Importantly, domain swapping has been observed for human cystatin C (HCC), a protein capable of forming amyloid deposits in brain arteries. In this study, the ability of short exposure to high-intensity X-ray radiation to induce domain swapping in solutions of several HCC variants (wild-type HCC and V57G, V57D, V57N, V57P, and L68V mutants) was determined. The study was conducted using time-resolved small-angle X-ray scattering (TR-SAXS) synchrotron radiation. The protein samples were also analysed using small-angle neutron scattering and NMR diffusometry. Exposing HCC to... (More)

Domain swapping is observed for many proteins with flexible conformations. This phenomenon is often associated with the development of conformational diseases. Importantly, domain swapping has been observed for human cystatin C (HCC), a protein capable of forming amyloid deposits in brain arteries. In this study, the ability of short exposure to high-intensity X-ray radiation to induce domain swapping in solutions of several HCC variants (wild-type HCC and V57G, V57D, V57N, V57P, and L68V mutants) was determined. The study was conducted using time-resolved small-angle X-ray scattering (TR-SAXS) synchrotron radiation. The protein samples were also analysed using small-angle neutron scattering and NMR diffusometry. Exposing HCC to synchrotron radiation (over 50 ms) led to a gradual increase in the dimeric fraction, and for exposures longer than 150 ms, the oligomer fraction was dominant. In contrast, the non-irradiated protein solutions, apart from the V57P variant, were predominantly monomeric (e.g., V57G) or in monomer/dimer equilibrium. This work might represent the first observation of domain swapping induced by high-intensity X-rays.

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author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
9
issue
1
article number
8548
publisher
Nature Publishing Group
external identifiers
  • scopus:85067287624
  • pmid:31189973
ISSN
2045-2322
DOI
10.1038/s41598-019-44811-1
language
English
LU publication?
no
id
98d331a8-f1be-4592-9ee6-cc2736799d03
date added to LUP
2019-06-26 10:20:16
date last changed
2024-07-10 23:13:37
@article{98d331a8-f1be-4592-9ee6-cc2736799d03,
  abstract     = {{<p>Domain swapping is observed for many proteins with flexible conformations. This phenomenon is often associated with the development of conformational diseases. Importantly, domain swapping has been observed for human cystatin C (HCC), a protein capable of forming amyloid deposits in brain arteries. In this study, the ability of short exposure to high-intensity X-ray radiation to induce domain swapping in solutions of several HCC variants (wild-type HCC and V57G, V57D, V57N, V57P, and L68V mutants) was determined. The study was conducted using time-resolved small-angle X-ray scattering (TR-SAXS) synchrotron radiation. The protein samples were also analysed using small-angle neutron scattering and NMR diffusometry. Exposing HCC to synchrotron radiation (over 50 ms) led to a gradual increase in the dimeric fraction, and for exposures longer than 150 ms, the oligomer fraction was dominant. In contrast, the non-irradiated protein solutions, apart from the V57P variant, were predominantly monomeric (e.g., V57G) or in monomer/dimer equilibrium. This work might represent the first observation of domain swapping induced by high-intensity X-rays.</p>}},
  author       = {{Taube, Michal and Pietralik, Zuzanna and Szymanska, Aneta and Szutkowski, Kosma and Clemens, Daniel and Grubb, Anders and Kozak, Maciej}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{The domain swapping of human cystatin C induced by synchrotron radiation}},
  url          = {{http://dx.doi.org/10.1038/s41598-019-44811-1}},
  doi          = {{10.1038/s41598-019-44811-1}},
  volume       = {{9}},
  year         = {{2019}},
}