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Cloning and characterisation of novel cystatins from elapid snake venom glands.
Biochimie. 2011 Apr; 93(4):659-68.B

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 10(4)-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.

Authors+Show Affiliations

The Queensland Institute of Medical Research, Herston, Brisbane, QLD, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21172403

Citation

Richards, Renée, et al. "Cloning and Characterisation of Novel Cystatins From Elapid Snake Venom Glands." Biochimie, vol. 93, no. 4, 2011, pp. 659-68.
Richards R, St Pierre L, Trabi M, et al. Cloning and characterisation of novel cystatins from elapid snake venom glands. Biochimie. 2011;93(4):659-68.
Richards, R., St Pierre, L., Trabi, M., Johnson, L. A., de Jersey, J., Masci, P. P., & Lavin, M. F. (2011). Cloning and characterisation of novel cystatins from elapid snake venom glands. Biochimie, 93(4), 659-68. https://doi.org/10.1016/j.biochi.2010.12.008
Richards R, et al. Cloning and Characterisation of Novel Cystatins From Elapid Snake Venom Glands. Biochimie. 2011;93(4):659-68. PubMed PMID: 21172403.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cloning and characterisation of novel cystatins from elapid snake venom glands. AU - Richards,Renée, AU - St Pierre,Liam, AU - Trabi,Manuela, AU - Johnson,Lambro A, AU - de Jersey,John, AU - Masci,Paul P, AU - Lavin,Martin F, Y1 - 2010/12/21/ PY - 2010/08/17/received PY - 2010/12/09/accepted PY - 2010/12/22/entrez PY - 2010/12/22/pubmed PY - 2011/7/8/medline SP - 659 EP - 68 JF - Biochimie JO - Biochimie VL - 93 IS - 4 N2 - 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 10(4)-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. SN - 1638-6183 UR - https://www.unboundmedicine.com/medline/citation/21172403/Cloning_and_characterisation_of_novel_cystatins_from_elapid_snake_venom_glands_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-9084(10)00448-7 DB - PRIME DP - Unbound Medicine ER -