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Cyclic trimer of human cystatin C, an amyloidogenic protein - Molecular dynamics and experimental studies

Chrabaszczewska, Magdalena; Maszota-Zieleniak, Martyna; Pietralik, Zuzanna; Taube, Michał; Rodziewicz-Motowidło, Sylwia; Szymańska, Aneta; Szutkowski, Kosma; Clemens, Daniel; Grubb, Anders LU and Kozak, Maciej (2018) In Journal of Applied Physics 123(17).
Abstract

Human cystatin C (HCC) is a cysteine protease inhibitor that takes a series of oligomeric forms in solution (e.g., dimers, trimers, tetramers, decamers, dodecamers, and other higher oligomers). The best-known form of cystatin C is the dimer, which arises as a result of a domain swapping mechanism. The formation of the HCC oligomeric forms, which is most likely due to this domain swapping mechanism, is associated with the aggregation of HCC into amyloid fibrils and deposits. To investigate the structure of a specific HCC oligomer, we developed a covalently stabilized trimer of HCC. An atomic model of this HCC trimer was proposed on the basis of molecular docking and molecular dynamics simulations. The most stable model of the HCC trimer... (More)

Human cystatin C (HCC) is a cysteine protease inhibitor that takes a series of oligomeric forms in solution (e.g., dimers, trimers, tetramers, decamers, dodecamers, and other higher oligomers). The best-known form of cystatin C is the dimer, which arises as a result of a domain swapping mechanism. The formation of the HCC oligomeric forms, which is most likely due to this domain swapping mechanism, is associated with the aggregation of HCC into amyloid fibrils and deposits. To investigate the structure of a specific HCC oligomer, we developed a covalently stabilized trimer of HCC. An atomic model of this HCC trimer was proposed on the basis of molecular docking and molecular dynamics simulations. The most stable model of the HCC trimer obtained from the molecular dynamics simulations is characterized by a well-preserved secondary structure. The molecular size and structural parameters of the HCC trimer in solution were also confirmed by Small Angle Neutron Scattering and Nuclear Magnetic Resonance Diffusometry.

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author
publishing date
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Contribution to journal
publication status
published
subject
in
Journal of Applied Physics
volume
123
issue
17
publisher
American Institute of Physics
external identifiers
  • scopus:85046881900
ISSN
0021-8979
DOI
10.1063/1.5023807
language
English
LU publication?
no
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f1293bc7-84b6-4101-876e-e262323aca80
date added to LUP
2018-05-23 15:38:05
date last changed
2019-08-14 04:17:03
@article{f1293bc7-84b6-4101-876e-e262323aca80,
  abstract     = {<p>Human cystatin C (HCC) is a cysteine protease inhibitor that takes a series of oligomeric forms in solution (e.g., dimers, trimers, tetramers, decamers, dodecamers, and other higher oligomers). The best-known form of cystatin C is the dimer, which arises as a result of a domain swapping mechanism. The formation of the HCC oligomeric forms, which is most likely due to this domain swapping mechanism, is associated with the aggregation of HCC into amyloid fibrils and deposits. To investigate the structure of a specific HCC oligomer, we developed a covalently stabilized trimer of HCC. An atomic model of this HCC trimer was proposed on the basis of molecular docking and molecular dynamics simulations. The most stable model of the HCC trimer obtained from the molecular dynamics simulations is characterized by a well-preserved secondary structure. The molecular size and structural parameters of the HCC trimer in solution were also confirmed by Small Angle Neutron Scattering and Nuclear Magnetic Resonance Diffusometry.</p>},
  articleno    = {174701},
  author       = {Chrabaszczewska, Magdalena and Maszota-Zieleniak, Martyna and Pietralik, Zuzanna and Taube, Michał and Rodziewicz-Motowidło, Sylwia and Szymańska, Aneta and Szutkowski, Kosma and Clemens, Daniel and Grubb, Anders and Kozak, Maciej},
  issn         = {0021-8979},
  language     = {eng},
  month        = {05},
  number       = {17},
  publisher    = {American Institute of Physics},
  series       = {Journal of Applied Physics},
  title        = {Cyclic trimer of human cystatin C, an amyloidogenic protein - Molecular dynamics and experimental studies},
  url          = {http://dx.doi.org/10.1063/1.5023807},
  volume       = {123},
  year         = {2018},
}