Refereed journal article or data article (A1)
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
List of Authors: Li-Li Li, Katryna Cisek, Michael J. Courtney
Publisher: FRONTIERS MEDIA SA
Publication year: 2017
Journal: Frontiers in Molecular Neuroscience
Journal name in source: FRONTIERS IN MOLECULAR NEUROSCIENCE
Journal acronym: FRONT MOL NEUROSCI
Article number: 58
Volume number: 10
Number of pages: 13
ISSN: 1662-5099
eISSN: 1662-5099
DOI: http://dx.doi.org/10.3389/fnmol.2017.00058
Self-archived copy’s web address: 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.
Downloadable publication This is an electronic reprint of the original article. |  |
