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

Magdalena Chrabąszczewska , Martyna Maszota-Zieleniak , Zuzanna Pietralik , Michał Taube , Sylwia Rodziewicz-Motowidło , Aneta Szymańska , Kosma Szutkowski , Daniel Clemens , Anders Grubb , Maciej Kozak


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.
Author Magdalena Chrabąszczewska
Magdalena Chrabąszczewska,,
, Martyna Maszota-Zieleniak PChM
Martyna Maszota-Zieleniak,,
- Laboratory of Medical Chemistry
, Zuzanna Pietralik
Zuzanna Pietralik,,
, Michał Taube
Michał Taube,,
, Sylwia Rodziewicz-Motowidło PChM
Sylwia Rodziewicz-Motowidło,,
- Laboratory of Medical Chemistry
, Aneta Szymańska PChM
Aneta Szymańska,,
- Laboratory of Medical Chemistry
, Kosma Szutkowski
Kosma Szutkowski,,
, Daniel Clemens
Daniel Clemens,,
, Anders Grubb
Anders Grubb,,
, Maciej Kozak
Maciej Kozak,,
Journal seriesJournal of Applied Physics, ISSN 0021-8979
Issue year2018
Languageen angielski
Score (nominal)35
ScoreMinisterial score = 30.0, 07-05-2018, ArticleFromJournal
Ministerial score (2013-2016) = 35.0, 07-05-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 2.068 (2) - 2016=2.103 (5)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.