Utilize este identificador para referenciar este registo:
https://hdl.handle.net/10316/103325
Campo DC | Valor | Idioma |
---|---|---|
dc.contributor.author | Luís, João P. | - |
dc.contributor.author | Mata, Ana I. | - |
dc.contributor.author | Simões, Carlos J. V. | - |
dc.contributor.author | Brito, Rui M. M. | - |
dc.date.accessioned | 2022-11-07T10:10:23Z | - |
dc.date.available | 2022-11-07T10:10:23Z | - |
dc.date.issued | 2022-02-26 | - |
dc.identifier.issn | 1422-0067 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/103325 | - |
dc.description.abstract | Interleukin-1 receptor type 1 (IL-1R1) is a key player in inflammation and immune responses. This receptor regulates IL-1 activity in two forms: as a membrane-bound form and as a soluble ectodomain. The details and differences between the conformational dynamics of the membrane-bound and the soluble IL-1R1 ectodomains (ECDs) remain largely elusive. Here, we study and compare the structural dynamics of the soluble and membrane-bound IL-1R1-ECDs using molecular dynamics (MD) simulations, focusing on the flexible interdomain linker of the ECD, as well as the spatial rearrangements between the Ig-like domains of the ECD. To explore the membrane-bound conformations, a full-length IL-1R1 structural model was developed and subjected to classical equilibrium MD. Comparative analysis of multiple MD trajectories of the soluble and the membrane-bound IL-1R1-ECDs reveals that (i) as somewhat expected, the extent of the visited "open-to-closed" transitional states differs significantly between the soluble and membrane-bound forms; (ii) the soluble form presents open-closed transitions, sampling a wider rotational motion between the Ig-like domains of the ECD, visiting closed and "twisted" conformations in higher extent, whereas the membrane-bound form is characterized by more conformationally restricted states; (iii) interestingly, the backbone dihedral angles of residues Glu202, Glu203 and Asn204, located in the flexible linker, display the highest variations during the transition between discrete conformational states detected in IL-1R1, thus appearing to work as the "central wheel of a clock's movement". The simulations and analyses presented in this contribution offer a deeper insight into the structure and dynamics of IL-1R1, which may be explored in a drug discovery setting. | pt |
dc.language.iso | eng | pt |
dc.relation | FCT - Ph.D. grant PD/BD/135292/2017 | pt |
dc.relation | FCT - Ph.D. grant PD/BD/135289/2017 | pt |
dc.relation | FCT - CPCA/A0/7316/2020 | pt |
dc.relation | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/QUI/00313/2019/PT | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | interleukin-1 | pt |
dc.subject | interleukin-1 receptor type 1 | pt |
dc.subject | flexible linker | pt |
dc.subject | molecular dynamics | pt |
dc.subject.mesh | Protein Conformation | pt |
dc.subject.mesh | Molecular Dynamics Simulation | pt |
dc.title | Conformational Dynamics of the Soluble and Membrane-Bound Forms of Interleukin-1 Receptor Type-1: Insights into Linker Flexibility and Domain Orientation | pt |
dc.type | article | - |
degois.publication.firstPage | 2599 | pt |
degois.publication.issue | 5 | pt |
degois.publication.title | International Journal of Molecular Sciences | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.3390/ijms23052599 | pt |
degois.publication.volume | 23 | pt |
dc.date.embargo | 2022-02-26 | * |
uc.date.periodoEmbargo | 0 | pt |
item.fulltext | Com Texto completo | - |
item.grantfulltext | open | - |
item.languageiso639-1 | en | - |
item.cerifentitytype | Publications | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
crisitem.project.grantno | Coimbra Chemistry Center | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.orcid | 0000-0003-2760-6996 | - |
crisitem.author.orcid | 0000-0002-9508-7035 | - |
crisitem.author.orcid | 0000-0001-5994-9104 | - |
crisitem.author.orcid | 0000-0001-9128-2557 | - |
Aparece nas coleções: | I&D CQC - Artigos em Revistas Internacionais |
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