dc.creator | García Guerrero, Estefanía | es |
dc.creator | Pérez Simón, José Antonio | es |
dc.creator | Sánchez Abarca, Luis Ignacio | es |
dc.creator | Díaz Moreno, Irene | es |
dc.creator | Rosa Acosta, Miguel Ángel de la | es |
dc.creator | Díaz Quintana, Antonio Jesús | es |
dc.date.accessioned | 2017-06-12T13:28:30Z | |
dc.date.available | 2017-06-12T13:28:30Z | |
dc.date.issued | 2016 | |
dc.identifier.citation | García Guerrero, E., Pérez Simón, J.A., Sánchez Abarca, L.I., Díaz Moreno, I., Rosa Acosta, M.Á.d.l. y Díaz Quintana, A. (2016). The Dynamics of the Human Leukocyte Antigen Head Domain Modulates Its Recognition by the T-Cell Receptor. PLoS One, 11 (4), e0154219.1-e0154219.18. | |
dc.identifier.issn | 1932-6203 | es |
dc.identifier.uri | http://hdl.handle.net/11441/61233 | |
dc.description.abstract | Generating the immune response requires the discrimination of peptides presented by the
human leukocyte antigen complex (HLA) through the T-cell receptor (TCR). However, how
a single amino acid substitution in the antigen bonded to HLA affects the response of T cells
remains uncertain. Hence, we used molecular dynamics computations to analyze the
molecular interactions between peptides, HLA and TCR. We compared immunologically
reactive complexes with non-reactive and weakly reactive complexes. MD trajectories were
produced to simulate the behavior of isolated components of the various p-HLA-TCR complexes.
Analysis of the fluctuations showed that p-HLA binding barely restrains TCR
motions, and mainly affects the CDR3 loops. Conversely, inactive p-HLA complexes displayed
significant drop in their dynamics when compared with its free versus ternary forms
(p-HLA-TCR). In agreement, the free non-reactive p-HLA complexes showed a lower
amount of salt bridges than the responsive ones. This resulted in differences between the
electrostatic potentials of reactive and inactive p-HLA species and larger vibrational entropies
in non-elicitor complexes. Analysis of the ternary p-HLA-TCR complexes also revealed
a larger number of salt bridges in the responsive complexes. To summarize, our computations
indicate that the affinity of each p-HLA complex towards TCR is intimately linked to
both, the dynamics of its free species and its ability to form specific intermolecular salt-bridges
in the ternary complexes. Of outstanding interest is the emerging concept of antigen
reactivity involving its interplay with the HLA head sidechain dynamics by rearranging its
salt-bridges. | es |
dc.description.sponsorship | España, Ministerio de Economía y Competitividad BFU2012-31670/BMC | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Public Library of Science | es |
dc.relation.ispartof | PLoS One, 11 (4), e0154219.1-e0154219.18. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | The Dynamics of the Human Leukocyte Antigen Head Domain Modulates Its Recognition by the T-Cell Receptor | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular | es |
dc.relation.projectID | info:eu-repo/grantAgreement/MINECO/BFU2012-31670/BMC | es |
dc.relation.publisherversion | http://dx.doi.org/10.1371/journal.pone.0154219 | es |
dc.identifier.doi | 10.1371/journal.pone.0154219 | es |
idus.format.extent | 19 p. | es |
dc.journaltitle | PLoS One | es |
dc.publication.volumen | 11 | es |
dc.publication.issue | 4 | es |
dc.publication.initialPage | e0154219.1 | es |
dc.publication.endPage | e0154219.18 | es |
dc.contributor.funder | Ministerio de Economía y Competitividad (MINECO). España | |