Näytä suppeat kuvailutiedot

dc.contributor.authorYlilauri, Mikko
dc.contributor.authorPentikäinen, Olli
dc.date.accessioned2012-10-23T04:51:43Z
dc.date.available2012-10-23T04:51:43Z
dc.date.issued2012
dc.identifier.citationYlilauri, M., & Pentikäinen, O. (2012). Structural Mechanism of N-Methyl-D-Aspartate Receptor Type 1 Partial Agonism. <em>PLoS One</em>, 7 (10), e47604. <a href="http://dx.doi.org/10.1371/journal.pone.0047604">doi:10.1371/journal.pone.0047604</a> Retrieved from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047604">http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047604</a>fi
dc.identifier.otherTUTKAID_52480
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/40059
dc.description.abstractN-methyl-D-aspartate (NMDA) receptors belong to a family of ionotropic glutamate receptors that contribute to the signal transmission in the central nervous system. NMDA receptors are heterotetramers that usually consist of two GluN1 and GluN2 monomers. The extracellular ligand-binding domain (LBD) of a monomer is comprised of discontinuous segments that form the functional domains D1 and D2. While the binding of a full agonist glycine to LBD of GluN1 is linked to cleft closure and subsequent ion-channel opening, partial agonists are known to activate the receptor only sub-maximally. Although the crystal structures of the LBD of related GluA2 receptor explain the mechanism for the partial agonism, structures of GluN1-LBD cannot distinguish the difference between full and partial agonists. It is, however, probable that the partial agonists of GluN1 alter the structure of the LBD in order to result in a different pharmacological response than seen with full agonists. In this study, we used molecular dynamics simulations to reveal an intermediate closure-stage for GluN1, which is unseen in crystal structures. According to our calculations, this intermediate closure is not a transient stage but an energetically stable conformation. Our results demonstrate that the partial agonist cannot exert firm GluN1-LBD closure, especially if there is even a small force that disrupts the LBD closure. Accordingly, this result suggests the importance of forces from the ion channel for the relationship between pharmacological response and the structure of the LBD of members of this receptor family.fi
dc.language.isoeng
dc.publisherPLOS
dc.relation.ispartofseriesPLoS One
dc.relation.urihttp://www.plosone.org/article/info:doi/10.1371/journal.pone.0047604
dc.subject.otherglutamate receptoren
dc.subject.otherpartial agonisten
dc.subject.othermolecular dynamicsen
dc.subject.otherglutamaattireseptorifi
dc.subject.otherpartiaalinen agonistifi
dc.subject.othermolekyylidynamiikkafi
dc.titleStructural Mechanism of N-Methyl-D-Aspartate Receptor Type 1 Partial Agonism
dc.typeArticle
dc.identifier.urnURN:NBN:fi:jyu-201210232753
dc.contributor.laitosBio- ja ympäristötieteiden laitosfi
dc.contributor.laitosDepartment of Biological and Environmental Scienceen
dc.contributor.oppiaineSolu- ja molekyylibiologiafi
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.identifier.doi10.1371/journal.pone.0047604
dc.date.updated2012-10-23T03:30:03Z
dc.type.coarjournal article
dc.description.reviewstatuspeerReviewed
dc.format.pagerangee47604
dc.relation.issn1932-6203
dc.relation.numberinseries10
dc.relation.volume7
dc.type.versionpublishedVersion
dc.rights.copyright© 2012 Ylilauri, Pentikäinen. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.accesslevelopenAccessfi
dc.rights.urlhttps://creativecommons.org/licenses/by/2.0/


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© 2012 Ylilauri, Pentikäinen. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Ellei muuten mainita, aineiston lisenssi on © 2012 Ylilauri, Pentikäinen. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.