Novel gamma-carboxyglutamic acid-containing peptides from the venom of Conus textile
(2006) In The FEBS Journal 273(12). p.2779-2788- Abstract
- The cone snail is the only invertebrate system in which the vitamin K-dependent carboxylase (or gamma-carboxylase) and its product gamma-carboxyglutamic acid (Gla) have been identified. It remains the sole source of structural information of invertebrate gamma-carboxylase substrates. Four novel Gla-containing peptides were purified from the venom of Conus textile and characterized using biochemical methods and mass spectrometry. The peptides Gla(1)-TxVI, Gla(2)-TxVI/A, Gla(2)-TxVI/B and Gla(3)-TxVI each have six Cys residues and belong to the O-superfamily of conotoxins. All four conopeptides contain 4-trans-hydroxyproline and the unusual amino acid 6-L >-bromotryptophan. Gla(2)-TxVI/A and Gla(2)-TxVI/B are isoforms with an amidated... (More)
- The cone snail is the only invertebrate system in which the vitamin K-dependent carboxylase (or gamma-carboxylase) and its product gamma-carboxyglutamic acid (Gla) have been identified. It remains the sole source of structural information of invertebrate gamma-carboxylase substrates. Four novel Gla-containing peptides were purified from the venom of Conus textile and characterized using biochemical methods and mass spectrometry. The peptides Gla(1)-TxVI, Gla(2)-TxVI/A, Gla(2)-TxVI/B and Gla(3)-TxVI each have six Cys residues and belong to the O-superfamily of conotoxins. All four conopeptides contain 4-trans-hydroxyproline and the unusual amino acid 6-L >-bromotryptophan. Gla(2)-TxVI/A and Gla(2)-TxVI/B are isoforms with an amidated C-terminus that differ at positions +1 and +13. Three isoforms of Gla(3)-TxVI were observed that differ at position +7: Gla(3)-TxVI, Glu7-Gla(3)-TxVI and Asp7-Gla(3)-TxVI. The cDNAs encoding the precursors of the four peptides were cloned. The predicted signal sequences (amino acids -46 to -27) were nearly identical and highly hydrophobic. The predicted propeptide region (-20 to -1) that contains the gamma-carboxylation recognition site (gamma-CRS) is very similar in Gla(2)-TxVI/A, Gla(2)-TxVI/B and Gla(3)-TxVI, but is more divergent for Gla(1)-TxVI. Kinetic studies utilizing the Conus gamma-carboxylase and synthetic peptide substrates localized the gamma-CRS of Gla(1)-TxVI to the region -14 to -1 of the polypeptide precursor: the K-m was reduced from 1.8 mM for Gla (1)-TxVI lacking a propeptide to 24 mu M when a 14-residue propeptide was attached to the substrate. Similarly, addition of an 18-residue propeptide to Gla(2)-TxVI/B reduced the K-m value tenfold. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/407454
- author
- Czerwiec, E ; Kalume, DE ; Roepstorff, P ; Hambe, B ; Furie, B ; Furie, BC and Stenflo, Johan LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- vitamin K, propeptide, Conus textile, gamma-carboxyglutamic acid, conotoxin
- in
- The FEBS Journal
- volume
- 273
- issue
- 12
- pages
- 2779 - 2788
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000237954700017
- pmid:16817904
- scopus:33745199727
- ISSN
- 1742-464X
- DOI
- 10.1111/j.1742-4658.2006.05294.x
- language
- English
- LU publication?
- yes
- id
- 1a0f60b9-1f33-4a21-96dd-7ee728e635b9 (old id 407454)
- date added to LUP
- 2016-04-01 15:39:19
- date last changed
- 2022-05-08 04:48:27
@article{1a0f60b9-1f33-4a21-96dd-7ee728e635b9,
abstract = {{The cone snail is the only invertebrate system in which the vitamin K-dependent carboxylase (or gamma-carboxylase) and its product gamma-carboxyglutamic acid (Gla) have been identified. It remains the sole source of structural information of invertebrate gamma-carboxylase substrates. Four novel Gla-containing peptides were purified from the venom of Conus textile and characterized using biochemical methods and mass spectrometry. The peptides Gla(1)-TxVI, Gla(2)-TxVI/A, Gla(2)-TxVI/B and Gla(3)-TxVI each have six Cys residues and belong to the O-superfamily of conotoxins. All four conopeptides contain 4-trans-hydroxyproline and the unusual amino acid 6-L >-bromotryptophan. Gla(2)-TxVI/A and Gla(2)-TxVI/B are isoforms with an amidated C-terminus that differ at positions +1 and +13. Three isoforms of Gla(3)-TxVI were observed that differ at position +7: Gla(3)-TxVI, Glu7-Gla(3)-TxVI and Asp7-Gla(3)-TxVI. The cDNAs encoding the precursors of the four peptides were cloned. The predicted signal sequences (amino acids -46 to -27) were nearly identical and highly hydrophobic. The predicted propeptide region (-20 to -1) that contains the gamma-carboxylation recognition site (gamma-CRS) is very similar in Gla(2)-TxVI/A, Gla(2)-TxVI/B and Gla(3)-TxVI, but is more divergent for Gla(1)-TxVI. Kinetic studies utilizing the Conus gamma-carboxylase and synthetic peptide substrates localized the gamma-CRS of Gla(1)-TxVI to the region -14 to -1 of the polypeptide precursor: the K-m was reduced from 1.8 mM for Gla (1)-TxVI lacking a propeptide to 24 mu M when a 14-residue propeptide was attached to the substrate. Similarly, addition of an 18-residue propeptide to Gla(2)-TxVI/B reduced the K-m value tenfold.}},
author = {{Czerwiec, E and Kalume, DE and Roepstorff, P and Hambe, B and Furie, B and Furie, BC and Stenflo, Johan}},
issn = {{1742-464X}},
keywords = {{vitamin K; propeptide; Conus textile; gamma-carboxyglutamic acid; conotoxin}},
language = {{eng}},
number = {{12}},
pages = {{2779--2788}},
publisher = {{Wiley-Blackwell}},
series = {{The FEBS Journal}},
title = {{Novel gamma-carboxyglutamic acid-containing peptides from the venom of Conus textile}},
url = {{http://dx.doi.org/10.1111/j.1742-4658.2006.05294.x}},
doi = {{10.1111/j.1742-4658.2006.05294.x}},
volume = {{273}},
year = {{2006}},
}