Cloning and characterisation of novel cystatins from elapid snake venom glands

Richards, Renee, St Pierre, Liam, Trabi, Manuela, Johnson, Lambro A., de Jersey, John, Masci, Paul P. and Lavin, Martin F. (2011) Cloning and characterisation of novel cystatins from elapid snake venom glands. Biochimie, 93 4: 659-668. doi:10.1016/j.biochi.2010.12.008


Author Richards, Renee
St Pierre, Liam
Trabi, Manuela
Johnson, Lambro A.
de Jersey, John
Masci, Paul P.
Lavin, Martin F.
Title Cloning and characterisation of novel cystatins from elapid snake venom glands
Journal name Biochimie   Check publisher's open access policy
ISSN 0300-9084
1638-6183
Publication date 2011-04
Year available 2010
Sub-type Article (original research)
DOI 10.1016/j.biochi.2010.12.008
Open Access Status
Volume 93
Issue 4
Start page 659
End page 668
Total pages 10
Place of publication Paris, France
Publisher Elsevier
Collection year 2011
Language eng
Formatted abstract
Snake venoms contain a complex mixture of polypeptides that modulate prey homeostatic mechanisms through highly specific and targeted interactions. In this study we have identified and characterised cystatin-like cysteine-protease inhibitors from elapid snake venoms for the first time. Novel cystatin sequences were cloned from 12 of 13 elapid snake venom glands and the protein was detected, albeit at very low levels, in a total of 22 venoms. One highly conserved isoform, which displayed close sequence identity with family 2 cystatins, was detected in each elapid snake. Crude Austrelaps superbus (Australian lowland copperhead) snake venom inhibited papain, and a recombinant form of A. superbus cystatin inhibited cathepsin L ≅ papain > cathepsin B, with no inhibition observed for calpain or legumain. While snake venom cystatins have truncated N-termini, sequence alignment and structural modelling suggested that the evolutionarily conserved Gly-11 of family 2 cystatins, essential for cysteine protease inhibition, is conserved in snake venom cystatins as Gly-3. This was confirmed by mutagenesis at the Gly-3 site, which increased the dissociation constant for papain by 104-fold. These data demonstrate that elapid snake venom cystatins are novel members of the type 2 family. The widespread, low level expression of type 2 cystatins in snake venom, as well as the presence of only one highly conserved isoform in each species, imply essential housekeeping or regulatory roles for these proteins. © 2010 Elsevier Masson SAS. All rights reserved.
Keyword Cystatin
Cysteine-protease inhibitor
Elapid venom
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 21 December, 2010.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
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Created: Wed, 16 Feb 2011, 11:36:50 EST by Debbie Banks on behalf of School of Medicine