Identification of Conomarphin Variants in the <i>Conus eburneus</i> Venom and the Effect of Sequence and PTM Variations on Conomarphin Conformations

Marine cone snails belonging to the Conidae family make use of neuroactive peptides in their venom to capture prey. Here we report the proteome profile of the venom duct of <i>Conus eburneus</i>, a cone snail belonging to the Tesseliconus clade. Through tandem mass spectrometry and datab...

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Main Authors: Corazon Ericka Mae M. Itang, Jokent T. Gaza, Dan Jethro M. Masacupan, Dessa Camille R. Batoctoy, Yu-Ju Chen, Ricky B. Nellas, Eizadora T. Yu
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Marine Drugs
Subjects:
Online Access:https://www.mdpi.com/1660-3397/18/10/503
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spelling doaj-e04b9241e4b54ab3bb6ff8f10ed5eb312020-11-25T03:18:18ZengMDPI AGMarine Drugs1660-33972020-10-011850350310.3390/md18100503Identification of Conomarphin Variants in the <i>Conus eburneus</i> Venom and the Effect of Sequence and PTM Variations on Conomarphin ConformationsCorazon Ericka Mae M. Itang0Jokent T. Gaza1Dan Jethro M. Masacupan2Dessa Camille R. Batoctoy3Yu-Ju Chen4Ricky B. Nellas5Eizadora T. Yu6Institute of Chemistry, College of Science, University of the Philippines, Diliman, Quezon City 1101, PhilippinesInstitute of Chemistry, College of Science, University of the Philippines, Diliman, Quezon City 1101, PhilippinesMarine Science Institute, College of Science, University of the Philippines, Diliman, Quezon City 1101, PhilippinesInstitute of Chemistry, College of Science, University of the Philippines, Diliman, Quezon City 1101, PhilippinesInstitute of Chemistry, Academia Sinica, No. 128, Section 2, Academia Rd, Nankang, Taipei 115, TaiwanInstitute of Chemistry, College of Science, University of the Philippines, Diliman, Quezon City 1101, PhilippinesInstitute of Chemistry, College of Science, University of the Philippines, Diliman, Quezon City 1101, PhilippinesMarine cone snails belonging to the Conidae family make use of neuroactive peptides in their venom to capture prey. Here we report the proteome profile of the venom duct of <i>Conus eburneus</i>, a cone snail belonging to the Tesseliconus clade. Through tandem mass spectrometry and database searching against the <i>C. eburneus</i> transcriptome and the ConoServer database, we identified 24 unique conopeptide sequences in the venom duct. The majority of these peptides belong to the T and M gene superfamilies and are disulfide-bonded, with cysteine frameworks V, XIV, VI/VII, and III being the most abundant. All seven of the Cys-free peptides are conomarphin variants belonging to the M superfamily that eluted out as dominant peaks in the chromatogram. These conomarphins vary not only in amino acid residues in select positions along the backbone but also have one or more post-translational modifications (PTMs) such as proline hydroxylation, C-term amidation, and γ-carboxylation of glutamic acid. Using molecular dynamics simulations, the conomarphin variants were predicted to predominantly have hairpin-like or elongated structures in acidic pH. These two structures were found to have significant differences in electrostatic properties and the inclusion of PTMs seems to complement this disparity. The presence of polar PTMs (hydroxyproline and γ-carboxyglutamic acid) also appear to stabilize hydrogen bond networks in these conformations. Furthermore, these predicted structures are pH sensitive, becoming more spherical and compact at higher pH. The subtle conformational variations observed here might play an important role in the selection and binding of the peptides to their molecular targets.https://www.mdpi.com/1660-3397/18/10/503conopeptideproteomics3D structureconomarphins
collection DOAJ
language English
format Article
sources DOAJ
author Corazon Ericka Mae M. Itang
Jokent T. Gaza
Dan Jethro M. Masacupan
Dessa Camille R. Batoctoy
Yu-Ju Chen
Ricky B. Nellas
Eizadora T. Yu
spellingShingle Corazon Ericka Mae M. Itang
Jokent T. Gaza
Dan Jethro M. Masacupan
Dessa Camille R. Batoctoy
Yu-Ju Chen
Ricky B. Nellas
Eizadora T. Yu
Identification of Conomarphin Variants in the <i>Conus eburneus</i> Venom and the Effect of Sequence and PTM Variations on Conomarphin Conformations
Marine Drugs
conopeptide
proteomics
3D structure
conomarphins
author_facet Corazon Ericka Mae M. Itang
Jokent T. Gaza
Dan Jethro M. Masacupan
Dessa Camille R. Batoctoy
Yu-Ju Chen
Ricky B. Nellas
Eizadora T. Yu
author_sort Corazon Ericka Mae M. Itang
title Identification of Conomarphin Variants in the <i>Conus eburneus</i> Venom and the Effect of Sequence and PTM Variations on Conomarphin Conformations
title_short Identification of Conomarphin Variants in the <i>Conus eburneus</i> Venom and the Effect of Sequence and PTM Variations on Conomarphin Conformations
title_full Identification of Conomarphin Variants in the <i>Conus eburneus</i> Venom and the Effect of Sequence and PTM Variations on Conomarphin Conformations
title_fullStr Identification of Conomarphin Variants in the <i>Conus eburneus</i> Venom and the Effect of Sequence and PTM Variations on Conomarphin Conformations
title_full_unstemmed Identification of Conomarphin Variants in the <i>Conus eburneus</i> Venom and the Effect of Sequence and PTM Variations on Conomarphin Conformations
title_sort identification of conomarphin variants in the <i>conus eburneus</i> venom and the effect of sequence and ptm variations on conomarphin conformations
publisher MDPI AG
series Marine Drugs
issn 1660-3397
publishDate 2020-10-01
description Marine cone snails belonging to the Conidae family make use of neuroactive peptides in their venom to capture prey. Here we report the proteome profile of the venom duct of <i>Conus eburneus</i>, a cone snail belonging to the Tesseliconus clade. Through tandem mass spectrometry and database searching against the <i>C. eburneus</i> transcriptome and the ConoServer database, we identified 24 unique conopeptide sequences in the venom duct. The majority of these peptides belong to the T and M gene superfamilies and are disulfide-bonded, with cysteine frameworks V, XIV, VI/VII, and III being the most abundant. All seven of the Cys-free peptides are conomarphin variants belonging to the M superfamily that eluted out as dominant peaks in the chromatogram. These conomarphins vary not only in amino acid residues in select positions along the backbone but also have one or more post-translational modifications (PTMs) such as proline hydroxylation, C-term amidation, and γ-carboxylation of glutamic acid. Using molecular dynamics simulations, the conomarphin variants were predicted to predominantly have hairpin-like or elongated structures in acidic pH. These two structures were found to have significant differences in electrostatic properties and the inclusion of PTMs seems to complement this disparity. The presence of polar PTMs (hydroxyproline and γ-carboxyglutamic acid) also appear to stabilize hydrogen bond networks in these conformations. Furthermore, these predicted structures are pH sensitive, becoming more spherical and compact at higher pH. The subtle conformational variations observed here might play an important role in the selection and binding of the peptides to their molecular targets.
topic conopeptide
proteomics
3D structure
conomarphins
url https://www.mdpi.com/1660-3397/18/10/503
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