Show simple item record

dc.contributor.authorLi L-L
dc.contributor.authorCisek K
dc.contributor.authorCourtney MJ
dc.date.accessioned2017-09-29T12:24:33Z
dc.date.available2017-09-29T12:24:33Z
dc.date.issued2017
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/4344
dc.description.abstractNeuronal nitric oxide synthase is widely regarded as an important contributor to a number of disorders of excitable tissues. Recently the adaptor protein NOS1AP has emerged as a contributor to several nNOS-linked conditions. As a consequence, the unexpectedly complex mechanisms of interaction between nNOS and its effector NOS1AP have become a particularly interesting topic from the point of view of both basic research and the potential for therapeutic applications. Here we demonstrate that the concerted action of two previously described motif regions contributing to the interaction of nNOS with NOS1AP, the ExF region and the PDZ ligand motif, efficiently excludes an alternate ligand from the nNOS-PDZ ligand-binding pocket. Moreover, we identify an additional element with a denaturable structure that contributes to interaction of NOS1AP with nNOS. Denaturation does not affect the functions of the individual motifs and results in a relatively mild drop, ∼3-fold, of overall binding affinity of the C-terminal region of NOS1AP for nNOS. However, denaturation selectively prevents the concerted action of the two motifs that normally results in efficient occlusion of the PDZ ligand-binding pocket, and results in 30-fold reduction of competition between NOS1AP and an alternate PDZ ligand.en
dc.language.isoENen
dc.publisherFrontiers Media SAen
dc.relation.ispartofseriesFrontiers in Molecular Neuroscienceen
dc.relation.urihttp://dx.doi.org/10.3389/fnmol.2017.00058en
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/en
dc.titleEfficient binding of the NOS1AP C-terminus to the nNOS PDZ pocket requires the concerted action of the PDZ ligand motif, the internal ExF site and structural integrity of an independent elementen
dc.description.versionpublished versionen
dc.contributor.departmentA.I. Virtanen -instituutti / Neurobiologiaen
uef.solecris.id46656674en
dc.type.publicationinfo:eu-repo/semantics/articleen
dc.rights.accessrights© Authorsen
dc.relation.doi10.3389/fnmol.2017.00058en
dc.description.reviewstatuspeerRevieweden
dc.relation.articlenumber58en
dc.relation.issn1662-5099en
dc.relation.volume10en
dc.rights.accesslevelopenAccessen
dc.type.okmA1en
dc.type.versioninfo:eu-repo/semantics/publishedVersionen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record