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dc.date.accessioned2017-08-09T10:09:34Z
dc.date.available2017-08-09T10:09:34Z
dc.date.created2013-11-26T16:43:16Z
dc.date.issued2013
dc.identifier.citationBjerregaard-Andersen, Kaare Perdreau, Harmonie Guldsten, Hanne Praetorius, Jeppe Jensen, Jan K. Morth, Jens Preben . The N-terminal cytoplasmic region of NCBE displays features of an intrinsic disordered structure and represents a novel target for specific drug screening. Frontiers in Physiology. 2013, 4(320)
dc.identifier.urihttp://hdl.handle.net/10852/56917
dc.description.abstractThe sodium dependent bicarbonate transporter NCBE/NBCn2 is predominantly expressed in the central nervous system (CNS). The highest protein concentrations are found in the choroid plexus. The primary function of this integral plasma membrane transport protein is to regulate intracellular neuronal pH and also probably to maintain the pH homeostasis across the blood-cerebrospinal fluid barrier. NCBE is predicted to contain at least 10 transmembrane helices. The N- and C- termini are both cytoplasmic, with a large N-terminal domain (Nt-NCBE) and a relatively small C-terminal domain (Ct-NCBE). The Nt-NCBE is likely to be involved in bicarbonate recognition and transport and contains key areas of regulation involving pH sensing and protein-protein interactions. Intrinsic disordered protein regions (IDPRs) are defined as protein regions having no rigid three-dimensional structure under physiological conditions. They are believed to be involved in signaling networks in which specific, low affinity, protein-protein interactions play an important role. We predict that NCBE and other SoLute Carrier 4 (SLC4) family members have a high level of intrinsic disorder in their cytoplasmic regions. To provide biophysical evidence for the IDPRs predicted in Nt-NCBE, we produced pure (>99%), recombinant Nt-NCBE using E. coli as the expression host. The protein was used to perform differential scanning fluorescence spectroscopy (DSF), in order to search for small molecules that would induce secondary or tertiary structure in the IDPRs. We expect this to assist the development of selective pharmaceutical compounds against individual SLC4 family members. We have also determined a low resolution (4 Å) X-ray crystal structure of the N-terminal core domain. The N-terminal cytoplasmic domain (cdb3) of anion exchanger 1 (AE1) shares a similar fold with the N-terminal core domain of NCBE. Crystallization conditions for the full-length N-terminal domain have been sought, but only the core domain yields diffracting crystals.en_US
dc.languageEN
dc.publisherFrontiers Research Foundation
dc.rightsAttribution 3.0 Unported
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/
dc.titleThe N-terminal cytoplasmic region of NCBE displays features of an intrinsic disordered structure and represents a novel target for specific drug screeningen_US
dc.typeJournal articleen_US
dc.creator.authorBjerregaard-Andersen, Kaare
dc.creator.authorPerdreau, Harmonie
dc.creator.authorGuldsten, Hanne
dc.creator.authorPraetorius, Jeppe
dc.creator.authorJensen, Jan K.
dc.creator.authorMorth, Jens Preben
cristin.unitcode185,29,22,0
cristin.unitnameCentre for Molecular Medicine Norway - Nordic EMBL Partnership
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1069679
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Frontiers in Physiology&rft.volume=4&rft.spage=&rft.date=2013
dc.identifier.jtitleFrontiers in Physiology
dc.identifier.volume4
dc.identifier.issue320
dc.identifier.pagecount9
dc.identifier.doihttp://dx.doi.org/10.3389/fphys.2013.00320
dc.identifier.urnURN:NBN:no-59561
dc.subject.nviVDP::Medisinsk molekylærbiologi: 711
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn1664-042X
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/56917/1/fphys-04-00320.pdf
dc.type.versionPublishedVersion


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