On the role of protein disulfide isomerase in the retrograde cell transport of secreted phospholipases A2

PloS One
Jernej OberčkalIgor Krizaj

Abstract

Following the finding that ammodytoxin (Atx), a neurotoxic secreted phospholipase A2 (sPLA2) in snake venom, binds specifically to protein disulfide isomerase (PDI) in vitro we show that these proteins also interact in living rat PC12 cells that are able to internalize this group IIA (GIIA) sPLA2. Atx and PDI co-localize in both differentiated and non-differentiated PC12 cells, as shown by fluorescence microscopy. Based on a model of the complex between Atx and yeast PDI (yPDI), a three-dimensional model of the complex between Atx and human PDI (hPDI) was constructed. The Atx binding site on hPDI is situated between domains b and b'. Atx interacts hPDI with an extensive area on its interfacial binding surface. The mammalian GIB, GIIA, GV and GX sPLA2s have the same fold as Atx. The first three sPLA2s have been detected intracellularly but not the last one. The models of their complexes with hPDI were constructed by replacement of Atx with the respective mammalian sPLA2 in the Atx-hPDI complex and molecular docking of the structures. According to the generated models, mammalian GIB, GIIA and GV sPLA2s form complexes with hPDI very similar to that with Atx. The contact area between GX sPLA2 and hPDI is however different from that...Continue Reading

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Citations

Apr 4, 2017·Computational Biology and Chemistry·Panchada Ch V GovinduKonkallu Hanumae Gowd
Nov 28, 2016·Archives of Biochemistry and Biophysics·Ana Iochabel Soares Moretti, Francisco Rafael Martins Laurindo
Jun 28, 2017·Toxicon : Official Journal of the International Society on Toxinology·Nai-Yong LiuJia-Ying Zhu

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Software Mentioned

PyMOL
HADDOCK
ImageJ
Zeiss ZEN
JACoP

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