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dc.contributor.advisorCaterina, Michael J.
dc.creatorGilchrist, John Michael
dc.date.accessioned2018-05-22T03:38:07Z
dc.date.available2018-05-22T03:38:07Z
dc.date.created2017-12
dc.date.issued2017-04-11
dc.date.submittedDecember 2017
dc.identifier.urihttp://jhir.library.jhu.edu/handle/1774.2/58608
dc.description.abstractThe voltage-gated sodium (Nav) channel complex is comprised of a channel-forming, ion-conducting alpha-subunit and one or multiple accessory beta-subunits. The latter has been shown to influence the function of Nav channels and mutations within the beta-subunit have been tied to cardiac and neurologic disorders. We show here that beta-subunits can also affect the pharmacology of Nav channels, particularly in relation to toxins derived from animal venoms. In this work we combine our knowledge of toxin binding sites with novel crystal structures of two beta-subunits to determine the cysteine residues responsible for forming the disulfide bridge between the beta2/beta4 subunits and the Nav1.2 channel. In doing so, we provide a basis for understanding the interaction between the beta-subunits and Nav channels and the functional consequences of this interaction.
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherJohns Hopkins University
dc.subjectVoltage-gated sodium channels
dc.subjectbeta-subunits
dc.subjectanimal toxins
dc.titleARCHITECTURE OF THE BETA2/BETA4-NAV CHANNEL SIGNALING COMPLEX
dc.typeThesis
thesis.degree.disciplinePhysiology
thesis.degree.grantorJohns Hopkins University
thesis.degree.grantorSchool of Medicine
thesis.degree.levelDoctoral
thesis.degree.namePh.D.
dc.date.updated2018-05-22T03:38:07Z
dc.type.materialtext
thesis.degree.departmentCellular and Molecular Physiology
dc.contributor.committeeMemberBosmans, Frank
dc.contributor.committeeMemberNathans, Jeremy
dc.contributor.committeeMemberSwartz, Kenton
dc.publisher.countryUSA
dc.creator.orcid0000-0002-9993-1387


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