Cargando…

Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93

The transmembrane glycoprotein CD93 has been identified as a potential new target to inhibit tumor angiogenesis. Recently, Multimerin-2 (MMRN2), a pan-endothelial extracellular matrix protein, has been identified as a ligand for CD93, but the interaction mechanism between these two proteins is yet t...

Descripción completa

Detalles Bibliográficos
Autores principales: Cicaloni, Vittoria, Karmakar, Malancha, Frusciante, Luisa, Pettini, Francesco, Visibelli, Anna, Orlandini, Maurizio, Galvagni, Federico, Mongiat, Maurizio, Silk, Michael, Nardi, Federica, Ascher, David, Santucci, Annalisa, Spiga, Ottavia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9638713/
https://www.ncbi.nlm.nih.gov/pubmed/36353214
http://dx.doi.org/10.3389/fbinf.2022.891553
_version_ 1784825483586699264
author Cicaloni, Vittoria
Karmakar, Malancha
Frusciante, Luisa
Pettini, Francesco
Visibelli, Anna
Orlandini, Maurizio
Galvagni, Federico
Mongiat, Maurizio
Silk, Michael
Nardi, Federica
Ascher, David
Santucci, Annalisa
Spiga, Ottavia
author_facet Cicaloni, Vittoria
Karmakar, Malancha
Frusciante, Luisa
Pettini, Francesco
Visibelli, Anna
Orlandini, Maurizio
Galvagni, Federico
Mongiat, Maurizio
Silk, Michael
Nardi, Federica
Ascher, David
Santucci, Annalisa
Spiga, Ottavia
author_sort Cicaloni, Vittoria
collection PubMed
description The transmembrane glycoprotein CD93 has been identified as a potential new target to inhibit tumor angiogenesis. Recently, Multimerin-2 (MMRN2), a pan-endothelial extracellular matrix protein, has been identified as a ligand for CD93, but the interaction mechanism between these two proteins is yet to be studied. In this article, we aim to investigate the structural and functional effects of induced mutations on the binding domain of CD93 to MMRN2. Starting from experimental data, we assessed how specific mutations in the C-type lectin-like domain (CTLD) affect the binding interaction profile. We described a four-step workflow in order to predict the effects of variations on the inter-residue interaction network at the PPI, based on evolutionary information, complex network metrics, and energetic affinity. We showed that the application of computational approaches, combined with experimental data, allowed us to gain more in-depth molecular insights into the CD93–MMRN2 interaction, offering a platform for developing innovative therapeutics able to target these molecules and block their interaction. This comprehensive molecular insight might prove useful in drug design in cancer therapy.
format Online
Article
Text
id pubmed-9638713
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-96387132022-11-08 Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93 Cicaloni, Vittoria Karmakar, Malancha Frusciante, Luisa Pettini, Francesco Visibelli, Anna Orlandini, Maurizio Galvagni, Federico Mongiat, Maurizio Silk, Michael Nardi, Federica Ascher, David Santucci, Annalisa Spiga, Ottavia Front Bioinform Bioinformatics The transmembrane glycoprotein CD93 has been identified as a potential new target to inhibit tumor angiogenesis. Recently, Multimerin-2 (MMRN2), a pan-endothelial extracellular matrix protein, has been identified as a ligand for CD93, but the interaction mechanism between these two proteins is yet to be studied. In this article, we aim to investigate the structural and functional effects of induced mutations on the binding domain of CD93 to MMRN2. Starting from experimental data, we assessed how specific mutations in the C-type lectin-like domain (CTLD) affect the binding interaction profile. We described a four-step workflow in order to predict the effects of variations on the inter-residue interaction network at the PPI, based on evolutionary information, complex network metrics, and energetic affinity. We showed that the application of computational approaches, combined with experimental data, allowed us to gain more in-depth molecular insights into the CD93–MMRN2 interaction, offering a platform for developing innovative therapeutics able to target these molecules and block their interaction. This comprehensive molecular insight might prove useful in drug design in cancer therapy. Frontiers Media S.A. 2022-06-21 /pmc/articles/PMC9638713/ /pubmed/36353214 http://dx.doi.org/10.3389/fbinf.2022.891553 Text en Copyright © 2022 Cicaloni, Karmakar, Frusciante, Pettini, Visibelli, Orlandini, Galvagni, Mongiat, Silk, Nardi, Ascher, Santucci and Spiga. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioinformatics
Cicaloni, Vittoria
Karmakar, Malancha
Frusciante, Luisa
Pettini, Francesco
Visibelli, Anna
Orlandini, Maurizio
Galvagni, Federico
Mongiat, Maurizio
Silk, Michael
Nardi, Federica
Ascher, David
Santucci, Annalisa
Spiga, Ottavia
Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93
title Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93
title_full Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93
title_fullStr Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93
title_full_unstemmed Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93
title_short Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93
title_sort bioinformatics approaches to predict mutation effects in the binding site of the proangiogenic molecule cd93
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9638713/
https://www.ncbi.nlm.nih.gov/pubmed/36353214
http://dx.doi.org/10.3389/fbinf.2022.891553
work_keys_str_mv AT cicalonivittoria bioinformaticsapproachestopredictmutationeffectsinthebindingsiteoftheproangiogenicmoleculecd93
AT karmakarmalancha bioinformaticsapproachestopredictmutationeffectsinthebindingsiteoftheproangiogenicmoleculecd93
AT fruscianteluisa bioinformaticsapproachestopredictmutationeffectsinthebindingsiteoftheproangiogenicmoleculecd93
AT pettinifrancesco bioinformaticsapproachestopredictmutationeffectsinthebindingsiteoftheproangiogenicmoleculecd93
AT visibellianna bioinformaticsapproachestopredictmutationeffectsinthebindingsiteoftheproangiogenicmoleculecd93
AT orlandinimaurizio bioinformaticsapproachestopredictmutationeffectsinthebindingsiteoftheproangiogenicmoleculecd93
AT galvagnifederico bioinformaticsapproachestopredictmutationeffectsinthebindingsiteoftheproangiogenicmoleculecd93
AT mongiatmaurizio bioinformaticsapproachestopredictmutationeffectsinthebindingsiteoftheproangiogenicmoleculecd93
AT silkmichael bioinformaticsapproachestopredictmutationeffectsinthebindingsiteoftheproangiogenicmoleculecd93
AT nardifederica bioinformaticsapproachestopredictmutationeffectsinthebindingsiteoftheproangiogenicmoleculecd93
AT ascherdavid bioinformaticsapproachestopredictmutationeffectsinthebindingsiteoftheproangiogenicmoleculecd93
AT santucciannalisa bioinformaticsapproachestopredictmutationeffectsinthebindingsiteoftheproangiogenicmoleculecd93
AT spigaottavia bioinformaticsapproachestopredictmutationeffectsinthebindingsiteoftheproangiogenicmoleculecd93