Cargando…
Extended disorder at the cell surface: The conformational landscape of the ectodomains of syndecans
Syndecans are membrane proteoglycans regulating extracellular matrix assembly, cell adhesion and signaling. Their ectodomains can be shed from the cell surface, and act as paracrine and autocrine effectors or as competitors of full-length syndecans. We report the first biophysical characterization o...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416954/ https://www.ncbi.nlm.nih.gov/pubmed/34505054 http://dx.doi.org/10.1016/j.mbplus.2021.100081 |
_version_ | 1783748285464313856 |
---|---|
author | Gondelaud, Frank Bouakil, Mathilde Le Fèvre, Aurélien Miele, Adriana Erica Chirot, Fabien Duclos, Bertrand Liwo, Adam Ricard-Blum, Sylvie |
author_facet | Gondelaud, Frank Bouakil, Mathilde Le Fèvre, Aurélien Miele, Adriana Erica Chirot, Fabien Duclos, Bertrand Liwo, Adam Ricard-Blum, Sylvie |
author_sort | Gondelaud, Frank |
collection | PubMed |
description | Syndecans are membrane proteoglycans regulating extracellular matrix assembly, cell adhesion and signaling. Their ectodomains can be shed from the cell surface, and act as paracrine and autocrine effectors or as competitors of full-length syndecans. We report the first biophysical characterization of the recombinant ectodomains of the four human syndecans using biophysical techniques, and show that they behave like flexible random-coil intrinsically disordered proteins, and adopt several conformation ensembles in solution. We have characterized their conformational landscapes using native mass spectrometry (MS) and ion-mobility MS, and demonstrated that the syndecan ectodomains explore the majority of their conformational landscape, from minor compact, globular-like, conformations to extended ones. We also report that the ectodomain of syndecan-4, corresponding to a natural isoform, is able to dimerize via a disulfide bond. We have generated a three-dimensional model of the C-terminus of this dimer, which supports the dimerization via a disulfide bond. Furthermore, we have mapped the NXIP adhesion motif of syndecans and their sequences involved in the formation of ternary complexes with integrins and growth factor receptors on the major conformations of their ectodomains, and shown that these sequences are not accessible in all the conformations, suggesting that only some of them are biologically active. Lastly, although the syndecan ectodomains have a far lower number of amino acid residues than their membrane partners, their intrinsic disorder and flexibility allow them to adopt extended conformations, which have roughly the same size as the cell surface receptors (e.g., integrins and growth factor receptors) they bind to. |
format | Online Article Text |
id | pubmed-8416954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-84169542021-09-08 Extended disorder at the cell surface: The conformational landscape of the ectodomains of syndecans Gondelaud, Frank Bouakil, Mathilde Le Fèvre, Aurélien Miele, Adriana Erica Chirot, Fabien Duclos, Bertrand Liwo, Adam Ricard-Blum, Sylvie Matrix Biol Plus Special Section on Molecular and Supramolecular structure of the extracellular matrix; Edited by Sylvie Ricard-Blum. Syndecans are membrane proteoglycans regulating extracellular matrix assembly, cell adhesion and signaling. Their ectodomains can be shed from the cell surface, and act as paracrine and autocrine effectors or as competitors of full-length syndecans. We report the first biophysical characterization of the recombinant ectodomains of the four human syndecans using biophysical techniques, and show that they behave like flexible random-coil intrinsically disordered proteins, and adopt several conformation ensembles in solution. We have characterized their conformational landscapes using native mass spectrometry (MS) and ion-mobility MS, and demonstrated that the syndecan ectodomains explore the majority of their conformational landscape, from minor compact, globular-like, conformations to extended ones. We also report that the ectodomain of syndecan-4, corresponding to a natural isoform, is able to dimerize via a disulfide bond. We have generated a three-dimensional model of the C-terminus of this dimer, which supports the dimerization via a disulfide bond. Furthermore, we have mapped the NXIP adhesion motif of syndecans and their sequences involved in the formation of ternary complexes with integrins and growth factor receptors on the major conformations of their ectodomains, and shown that these sequences are not accessible in all the conformations, suggesting that only some of them are biologically active. Lastly, although the syndecan ectodomains have a far lower number of amino acid residues than their membrane partners, their intrinsic disorder and flexibility allow them to adopt extended conformations, which have roughly the same size as the cell surface receptors (e.g., integrins and growth factor receptors) they bind to. Elsevier 2021-07-19 /pmc/articles/PMC8416954/ /pubmed/34505054 http://dx.doi.org/10.1016/j.mbplus.2021.100081 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Special Section on Molecular and Supramolecular structure of the extracellular matrix; Edited by Sylvie Ricard-Blum. Gondelaud, Frank Bouakil, Mathilde Le Fèvre, Aurélien Miele, Adriana Erica Chirot, Fabien Duclos, Bertrand Liwo, Adam Ricard-Blum, Sylvie Extended disorder at the cell surface: The conformational landscape of the ectodomains of syndecans |
title | Extended disorder at the cell surface: The conformational landscape of the ectodomains of syndecans |
title_full | Extended disorder at the cell surface: The conformational landscape of the ectodomains of syndecans |
title_fullStr | Extended disorder at the cell surface: The conformational landscape of the ectodomains of syndecans |
title_full_unstemmed | Extended disorder at the cell surface: The conformational landscape of the ectodomains of syndecans |
title_short | Extended disorder at the cell surface: The conformational landscape of the ectodomains of syndecans |
title_sort | extended disorder at the cell surface: the conformational landscape of the ectodomains of syndecans |
topic | Special Section on Molecular and Supramolecular structure of the extracellular matrix; Edited by Sylvie Ricard-Blum. |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416954/ https://www.ncbi.nlm.nih.gov/pubmed/34505054 http://dx.doi.org/10.1016/j.mbplus.2021.100081 |
work_keys_str_mv | AT gondelaudfrank extendeddisorderatthecellsurfacetheconformationallandscapeoftheectodomainsofsyndecans AT bouakilmathilde extendeddisorderatthecellsurfacetheconformationallandscapeoftheectodomainsofsyndecans AT lefevreaurelien extendeddisorderatthecellsurfacetheconformationallandscapeoftheectodomainsofsyndecans AT mieleadrianaerica extendeddisorderatthecellsurfacetheconformationallandscapeoftheectodomainsofsyndecans AT chirotfabien extendeddisorderatthecellsurfacetheconformationallandscapeoftheectodomainsofsyndecans AT duclosbertrand extendeddisorderatthecellsurfacetheconformationallandscapeoftheectodomainsofsyndecans AT liwoadam extendeddisorderatthecellsurfacetheconformationallandscapeoftheectodomainsofsyndecans AT ricardblumsylvie extendeddisorderatthecellsurfacetheconformationallandscapeoftheectodomainsofsyndecans |