Cyclic trimer of human cystatin C, an amyloidogenic protein - Molecular dynamics and experimental studies
(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
- Chrabaszczewska, Magdalena ; Maszota-Zieleniak, Martyna ; Pietralik, Zuzanna ; Taube, Michał ; Rodziewicz-Motowidło, Sylwia ; Szymańska, Aneta ; Szutkowski, Kosma ; Clemens, Daniel ; Grubb, Anders LU and Kozak, Maciej
- publishing date
- 2018-05-07
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Applied Physics
- volume
- 123
- issue
- 17
- article number
- 174701
- publisher
- American Institute of Physics (AIP)
- external identifiers
-
- scopus:85046881900
- ISSN
- 0021-8979
- DOI
- 10.1063/1.5023807
- language
- English
- LU publication?
- no
- id
- f1293bc7-84b6-4101-876e-e262323aca80
- date added to LUP
- 2018-05-23 15:38:05
- date last changed
- 2023-03-22 21:55:02
@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>}}, 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 (AIP)}}, 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}}, doi = {{10.1063/1.5023807}}, volume = {{123}}, year = {{2018}}, }