A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Efficient 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 Element
Tekijät: Li-Li Li, Katryna Cisek, Michael J. Courtney
Kustantaja: FRONTIERS MEDIA SA
Julkaisuvuosi: 2017
Journal: Frontiers in Molecular Neuroscience
Tietokannassa oleva lehden nimi: FRONTIERS IN MOLECULAR NEUROSCIENCE
Lehden akronyymi: FRONT MOL NEUROSCI
Artikkelin numero: 58
Vuosikerta: 10
Sivujen määrä: 13
ISSN: 1662-5099
eISSN: 1662-5099
DOI: https://doi.org/10.3389/fnmol.2017.00058
Verkko-osoite: 10.3389/fnmol.2017.00058
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/20519046
Neuronal 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, similar to 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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
