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Interactions of L-3,5,3'-Triiodothyronine, Allopregnanolone, and Ivermectin with the GABAA Receptor: Evidence for Overlapping Intersubunit Binding Modes

Descriptive

TypeOfResource
Text
TitleInfo
Title
Interactions of L-3,5,3'-Triiodothyronine, Allopregnanolone, and Ivermectin with the GABAA Receptor: Evidence for Overlapping Intersubunit Binding Modes
Name (type = personal)
NamePart (type = family)
Westergard
NamePart (type = given)
Thomas
Affiliation
Thomas Jefferson University
Role
RoleTerm (authority = marcrt); (type = text)
author
Name (type = personal)
NamePart (type = family)
Salari
NamePart (type = given)
Reza
Affiliation
Physics (Camden), Rutgers University
Role
RoleTerm (authority = marcrt); (type = text)
author
Name (authority = orcid); (authorityURI = http://id.loc.gov/vocabulary/identifiers/orcid.html); (type = personal); (valueURI = http://orcid.org/0000-0003-3757-3091)
NamePart (type = family)
Martin
NamePart (type = given)
Joseph V.
Affiliation
Biology, Rutgers University
Role
RoleTerm (authority = marcrt); (type = text)
author
Name (type = personal)
NamePart (type = family)
Brannigan
NamePart (type = given)
Grace
Affiliation
Physics (Camden), Rutgers University
Role
RoleTerm (authority = marcrt); (type = text)
author
Name (authority = RutgersOrg-School); (type = corporate)
NamePart
Camden College of Arts and Sciences
Name (authority = RutgersOrg-Department); (type = corporate)
NamePart
Biology
Name (authority = RutgersOrg-Department); (type = corporate)
NamePart
Physics (Camden)
Genre (authority = RULIB-FS)
Article, Refereed
Genre (authority = NISO JAV)
Version of Record (VoR)
Note (type = peerReview)
Peer reviewed
OriginInfo
DateIssued (encoding = w3cdtf); (keyDate = yes); (qualifier = exact)
2015
Publisher
Public Library of Science
Abstract (type = Abstract)
Structural mechanisms of modulation of γ-aminobutyric acid (GABA) type A receptors by neurosteroids and hormones remain unclear. The thyroid hormone L-3,5,3’-triiodothyronine (T3) inhibits GABA-A receptors at micromolar concentrations and has common features with neurosteroids such as allopregnanolone (ALLOP). Here we use functional experiments on α2β1γ2 GABA-A receptors expressed in Xenopus oocytes to detect competitive interactions between T3 and an agonist (ivermectin, IVM) with a crystallographically determined binding site at subunit interfaces in the transmembrane domain of a homologous receptor (glutamate-gated chloride channel, GluCl). T3 and ALLOP also show competitive effects, supporting the presence of both a T3 and ALLOP binding site at one or more subunit interfaces. Molecular dynamics (MD) simulations over 200 ns are used to investigate the dynamics and energetics of T3 in the identified intersubunit sites. In these simulations, T3 molecules occupying all intersubunit sites (with the exception of the α-β interface) display numerous energetically favorable conformations with multiple hydrogen bonding partners, including previously implicated polar/acidic sidechains and a structurally conserved deformation in the M1 backbone.
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
PhysicalDescription
InternetMediaType
application/pdf
Extent
18 p.
Subject (authority = local)
Topic
GABA-A
Subject (authority = LCSH)
Topic
GABA
Subject (authority = LCSH)
Topic
Thyroid hormones
Subject (authority = LCSH)
Topic
Triiodothyronine
Subject (authority = local)
Topic
Neurosteroids
Subject (authority = local)
Topic
Allopregnanolone
Subject (authority = LCSH)
Topic
Ivermectin
Extension
DescriptiveEvent
Type
Citation
DateTime (encoding = w3cdtf)
2015
AssociatedObject
Name
PLOS One
Type
Journal
Relationship
Has part
Detail
1-18
Identifier (type = volume and issue)
10(9)
Reference (type = url)
https://dx.doi.org/10.1371/journal.pone.0139072
Extension
DescriptiveEvent
Type
Grant award
AssociatedEntity
Role
Funder
Name
National Science Foundation
AssociatedEntity
Role
Originator
Name
Grace Brannigan
AssociatedEntity
Role
Originator
Name
Joseph V. Martin
AssociatedObject
Type
Grant number
Name
MCB1330728
RelatedItem (type = host)
TitleInfo
Title
Salari, Reza
Identifier (type = local)
rucore30183400001
RelatedItem (type = host)
TitleInfo
Title
Brannigan, Grace
Identifier (type = local)
rucore30183500001
RelatedItem (type = host)
TitleInfo
Title
Martin, Joseph V.
Identifier (type = local)
rucore30179300001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3VH5QTC
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Rights

RightsDeclaration (AUTHORITY = FS); (ID = rulibRdec0004)
Copyright for scholarly resources published in RUcore is retained by the copyright holder. By virtue of its appearance in this open access medium, you are free to use this resource, with proper attribution, in educational and other non-commercial settings. Other uses, such as reproduction or republication, may require the permission of the copyright holder.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsEvent
Type
Permission or license
AssociatedObject
Type
License
Name
Multiple author license v. 1
Detail
I hereby grant to Rutgers, The State University of New Jersey (Rutgers) the non-exclusive right to retain, reproduce, and distribute the deposited work (Work) in whole or in part, in and from its electronic format, without fee. This agreement does not represent a transfer of copyright to Rutgers.Rutgers may make and keep more than one copy of the Work for purposes of security, backup, preservation, and access and may migrate the Work to any medium or format for the purpose of preservation and access in the future. Rutgers will not make any alteration, other than as allowed by this agreement, to the Work.I represent and warrant to Rutgers that the Work is my original work. I also represent that the Work does not, to the best of my knowledge, infringe or violate any rights of others.I further represent and warrant that I have obtained all necessary rights to permit Rutgers to reproduce and distribute the Work and that any third-party owned content is clearly identified and acknowledged within the Work.By granting this license, I acknowledge that I have read and agreed to the terms of this agreement and all related RUcore and Rutgers policies.
RightsHolder (type = personal)
Name
FamilyName
Westergard
GivenName
Thomas
Role
Copyright holder
RightsHolder (type = personal)
Name
FamilyName
Salari
GivenName
Reza
Role
Copyright holder
RightsHolder (type = personal)
Name
FamilyName
Martin
GivenName
Joseph
MiddleName
V.
Role
Copyright holder
RightsHolder (type = personal)
Name
FamilyName
Brannigan
GivenName
Grace
Role
Copyright holder
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Technical

RULTechMD (ID = TECHNICAL1)
ContentModel
Document
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