Ion Selectivity and Gating in the NAK Channel

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Ion Selectivity and Gating in the NAK Channel

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dc.contributor.advisor Jiang, Youxing en
dc.creator Alam, Amer en
dc.date.accessioned 2010-07-12T18:10:51Z en
dc.date.available 2010-07-12T18:10:51Z en
dc.date.issued 2009-06-15 en
dc.identifier.other 754104989 en
dc.identifier.uri http://hdl.handle.net/2152.5/472 en
dc.description.abstract Ion selectivity and gating are two fundamental properties central to proper physiological functioning of ion channels. In this work, a thorough structural characterization of ion binding profiles is presented for the NaK channel, a non selective cation channel from Bacillus cereus, along with an analysis of channel opening and closing mechanisms. An introduction to the overall structure of the full length channel is presented along with initial characterization of its ion selectivity properties. The body of the thesis encompasses a detailed analysis of Ca2+ binding within NaK, followed by additional gating and selectivity studies using high resolution structures of a truncated form of the channel. Two Ca2+ binding sites are observed, both utilizing a unique Ca2+ chelation chemistry involving only backbone carbonyl groups as ligands, with Ca2+ selectivity at the extracellular site mediated by a through space interaction with a conserved acidic residue, Asp66, seen in other Ca2+ conducting channels. In the high resolution structure of the truncated NaK channel, we observe the intracellular gate in an open conformation much like that seen in MthK, making NaK the first channel for which both open and closed state structures are known. This is combined with a structural analysis of ion binding within the NaK selectivity filter, which reveals several interesting features that shed light on the possible underlying mechanisms of ion non-selectivity. en
dc.format.medium Electronic en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.subject Potassium Channels en
dc.subject Bacterial Proteins en
dc.subject Ion Channels en
dc.title Ion Selectivity and Gating in the NAK Channel en
dc.type.material Text en
dc.type.genre dissertation en
dc.format.digitalOrigin born digital en
thesis.degree.grantor Graduate School of Biomedical Sciences en
thesis.degree.department en
thesis.degree.name Doctor of Philosophy en
thesis.degree.level Ph.D en
thesis.degree.discipline Molecular Biophysics en
thesis.date.available 2011-06-15 en

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