Structural and functional interaction between domains in CFTR

Zitieren

Dateien zu dieser Ressource

Prüfsumme: MD5:ea5c5f3a250071f163d3bf263282dbd9

JAKŠEKOVIĆ, Inna, 2014. Structural and functional interaction between domains in CFTR [Dissertation]. Konstanz: University of Konstanz

@phdthesis{Jaksekovic2014Struc-29504, title={Structural and functional interaction between domains in CFTR}, year={2014}, author={Jakšeković, Inna}, address={Konstanz}, school={Universität Konstanz} }

Structural and functional interaction between domains in CFTR 2015-01-14T06:49:53Z 2015-01-14T06:49:53Z Jakšeković, Inna eng Jakšeković, Inna This work is related to structural and functional aspects of cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel whose dysfunction causes cystic fibrosis. The aim of the project was to test predictions made by structural models for CFTR about interactions between amino acid residues during the gating cycle.<br />The residues hypothesized to interact were studied with a cysteine-specific crosslinking approach: after their mutation to cysteine, the properties of resulting mutant CFTR were assayed upon the treatment with the cysteine-specific crosslinker bismaleimidoethane (BMOE).<br />Electrophysiological experiments suggest crosslinking between residues T164 and L1059, I266 and A969 (supported by biochemical evidence), and between G971 and S1049, implying a possible intramolecular interaction these residues are involved in. Crosslinking between F508C and R1070C might occur, too. Experiments with the pair G178/V260 did not give evidence of possible crosslinking between these residues or conformational changes of CFTR leading to the channel closure upon the crosslinker influence.<br />During erlectrophysiological experiments, intermittent fluctuations of the whole cell conductance were observed upon sulfhydryl-specific reagents, which could be related to possible activation of Ca2<sup>+</sup>-dependent Cl<sup>−</sup>channels (CaCC).<br />The approach applied in this work can provide evidence of structural proximity and functional interaction of amino acid residues belonging to different structural units of a protein, which information is essential for planning of future experiments and determining of drug discovery targets. 2014

Dateiabrufe seit 14.01.2015 (Informationen über die Zugriffsstatistik)

Jaksekovic_0-268990.pdf 194

Das Dokument erscheint in:

KOPS Suche


Stöbern

Mein Benutzerkonto