Spooner, Robert A. , Watson, Peter, Marsden, Catherine J., Smith, Daniel C., Moore, Katherine A. H., Cook, Jonathan P., Lord, Mike (J. Mike) and Roberts, L. M. (Lynne M.). (2004) Protein disulphide-isomerase reduces ricin to its A and B chains in the endoplasmic reticulum. Biochemical Journal, Vol.383 (No.2). pp. 285-293. ISSN 0264-6021

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Abstract

Cells expressing ricin B chain within the secretory pathway are significantly more resistant to intoxication by ricin holotoxin but not to other cytotoxins that exploit similar endocytic routes to the cytosol. Furthermore, cells expressing the related B chain of abrin are protected against both incoming abrin and ricin. These phenotypes can be correlated with the abilities of the respective B chains to form disulphide-linked A-B holotoxins, since abrin B chain forms heterodimers with either abrin or ricin A chains, whereas ricin B chain forms heterodimers with ricin A chain only. In the ricin B-expressing cells, this newly made lectin disappears with biphasic kinetics comprising a retention phase followed by slow turnover and disposal after disengagement from calnexin cycle components. Interference with ricin cytotoxicity occurs during the early retention phase when ricin B chain is associated with PDI (protein disulphide-isomerase). The data show that retrotranslocation of incoming toxin is impeded by PDI-catalysed formation of heterodimers between endogenous B and A chains derived from reduced holotoxin, thus proving that reduction of ricin occurs in the endoplasmic reticulum. In contrast with other toxins, ricin does not appear to require either proteolyfic cleavage or unfolding for PDI-catalysed reduction.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QH Natural history > QH426 Genetics Q Science > QP Physiology
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Oxidoreductases , Protein disulfide isomerase, Ricin, Toxins, Biochemistry, Endoplasmic reticulum, Reduction (Chemistry)
Journal or Publication Title:	Biochemical Journal
Publisher:	Portland Press Ltd.
ISSN:	0264-6021
Official Date:	15 October 2004
Volume:	Vol.383
Number:	No.2
Number of Pages:	9
Page Range:	pp. 285-293
Identification Number:	10.1042/BJ20040742
Status:	Peer Reviewed
Publication Status:	Published
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Wellcome Trust (London, England)
Grant number:	063058/Z/00/Z (WT), 059738/Z/99/Z (WT), 88/B16355 (BBSRC)
URI:	http://wrap.warwick.ac.uk/id/eprint/7838

Data sourced from Thomson Reuters' Web of Knowledge

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