Comparative modeling of hypothetical amyloid pores based on cylindrin

Verfasser / Beitragende:
[Magdalena Zulpo, Malgorzata Kotulska]
Ort, Verlag, Jahr:
2015
Enthalten in:
Journal of Molecular Modeling, 21/6(2015-06-01), 1-12
Format:
Artikel (online)
ID: 605511004
LEADER caa a22 4500
001 605511004
003 CHVBK
005 20210128100648.0
007 cr unu---uuuuu
008 210128e20150601xx s 000 0 eng
024 7 0 |a 10.1007/s00894-015-2691-4  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00894-015-2691-4 
245 0 0 |a Comparative modeling of hypothetical amyloid pores based on cylindrin  |h [Elektronische Daten]  |c [Magdalena Zulpo, Malgorzata Kotulska] 
520 3 |a Cylindrin is a six-stranded antiparallel beta barrel obtained from amyloidogenic strands of crystallin. It induces cell toxicity through an unknown mechanism. In this work, the potential use of the structure of cylindrin as a template for modeling amyloid pores—hypothetical transmembrane structures which appear during amyloid diseases—was studied. Using comparative modeling (performed by Modeller), we tested the stability of cylindrin-based pores made from several amyloid-forming and non-amyloid-forming strands deriving from mutated cylindrin and the prion sup35. We showed that cylindrin could be used as a template for modeling pores made from strands of amyloid proteins, but that the cylindrin structure does not result from the amyloidogenicity of these fragments, as fibril non-formers from the prion were also able to form a similar structure. Finally, we tested whether the cellular toxicity of cylindrin and related structures could be due to its incorporation into the cell membrane, leading to the creation of conducting ionic channels. The results of modeling indicate that cylindrin and tandem-repeat cylindrin,mutants of them, and cylindrin-like amyloid pores from prion sequences can only localize on the periphery of the membrane, and are not able to conduct any ions into the cell. These findings explain experimental results obtained for large unilamellar vesicles incubated with cylindrin, where conductance was not observed. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Amyloid  |2 nationallicence 
690 7 |a Amyloid channel  |2 nationallicence 
690 7 |a Cylindrin  |2 nationallicence 
690 7 |a Structure modeling  |2 nationallicence 
690 7 |a Comparative modeling  |2 nationallicence 
700 1 |a Zulpo  |D Magdalena  |u Department of Biomedical Engineering, Wroclaw University of Technology, ul. Wybrzeze Wyspianskiego 27, 50-370, Wroclaw, Poland  |4 aut 
700 1 |a Kotulska  |D Malgorzata  |u Department of Biomedical Engineering, Wroclaw University of Technology, ul. Wybrzeze Wyspianskiego 27, 50-370, Wroclaw, Poland  |4 aut 
773 0 |t Journal of Molecular Modeling  |d Springer Berlin Heidelberg  |g 21/6(2015-06-01), 1-12  |x 1610-2940  |q 21:6<1  |1 2015  |2 21  |o 894 
856 4 0 |u https://doi.org/10.1007/s00894-015-2691-4  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00894-015-2691-4  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zulpo  |D Magdalena  |u Department of Biomedical Engineering, Wroclaw University of Technology, ul. Wybrzeze Wyspianskiego 27, 50-370, Wroclaw, Poland  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kotulska  |D Malgorzata  |u Department of Biomedical Engineering, Wroclaw University of Technology, ul. Wybrzeze Wyspianskiego 27, 50-370, Wroclaw, Poland  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Journal of Molecular Modeling  |d Springer Berlin Heidelberg  |g 21/6(2015-06-01), 1-12  |x 1610-2940  |q 21:6<1  |1 2015  |2 21  |o 894