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Article: NMR structures and orientation of the fourth transmembrane domain of the rat divalent metal transporter (DMT1) with G185D mutation in SDS micelles

TitleNMR structures and orientation of the fourth transmembrane domain of the rat divalent metal transporter (DMT1) with G185D mutation in SDS micelles
Authors
KeywordsCD, DMT1
Micelle
NMR
Transmembrane peptide
Issue Date2005
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.wiley.com/journals
Citation
Biopolymers, 2005, v. 77 n. 4, p. 173-183 How to Cite?
AbstractDMT1, also known as Nramp2, is an iron transporter, and belongs to the family of Nramp proteins. Disease-causing mutations both in Nramp1 and Nramp2 occurring at the conserved two adjacent glycine residues located within the fourth transmembrane domain (TM4) suggest that TM4 may serve an important biological function. In the present study, we have determined the high-resolution structures of a synthetic peptide, corresponding to the sequence of the fourth transmembrane domain of rat DMT1 with G185D mutation, in membrane-mimetic environments (e.g., SDS micelles) using NMR spectroscopy and distance-geometry/simulated annealing calculations. The spatial structures showed a-helices without a kink in the middle portion of the peptide, with a highly flexible and poorly defined N-terminus. Both the N-terminus and the helical core of the peptide were embedded into the SDS micelles. Interestingly, the folding and membrane location of the C-terminus was pH dependent, being well-folded and inserted into SDS micelles only at a low pH value (4.0). The peptide exhibited amphipathic characteristics, with hydrophilic residues (Asp7, Thr11, Asp14, Asp14, and Thr 15) lying in one side of the helix, which provide a basis for the formation of water-filled channel architectures through self-associations. The significant broadening of the resonances of the hydrophilic residues Asp7, Thr11, and Asp14, which are buried inside SDS micelles, upon addition of Mn 2+ further verified the possibility of the formation of a channel through which metal ions pass. The substitution of Gly7 by an aspartate residue neither significantly altered the structure and membrane location of the peptide nor abolished its properties of channel forming and metal permeation compared with the wild-type peptide. © 2005 Wiley Periodicals, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/48524
ISSN
2015 Impact Factor: 2.248
2015 SCImago Journal Rankings: 1.199
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, Hen_HK
dc.contributor.authorLi, Fen_HK
dc.contributor.authorKwan, Men_HK
dc.contributor.authorHe, QYen_HK
dc.contributor.authorSun, Hen_HK
dc.date.accessioned2008-05-22T04:16:10Z-
dc.date.available2008-05-22T04:16:10Z-
dc.date.issued2005en_HK
dc.identifier.citationBiopolymers, 2005, v. 77 n. 4, p. 173-183en_HK
dc.identifier.issn0006-3525en_HK
dc.identifier.urihttp://hdl.handle.net/10722/48524-
dc.description.abstractDMT1, also known as Nramp2, is an iron transporter, and belongs to the family of Nramp proteins. Disease-causing mutations both in Nramp1 and Nramp2 occurring at the conserved two adjacent glycine residues located within the fourth transmembrane domain (TM4) suggest that TM4 may serve an important biological function. In the present study, we have determined the high-resolution structures of a synthetic peptide, corresponding to the sequence of the fourth transmembrane domain of rat DMT1 with G185D mutation, in membrane-mimetic environments (e.g., SDS micelles) using NMR spectroscopy and distance-geometry/simulated annealing calculations. The spatial structures showed a-helices without a kink in the middle portion of the peptide, with a highly flexible and poorly defined N-terminus. Both the N-terminus and the helical core of the peptide were embedded into the SDS micelles. Interestingly, the folding and membrane location of the C-terminus was pH dependent, being well-folded and inserted into SDS micelles only at a low pH value (4.0). The peptide exhibited amphipathic characteristics, with hydrophilic residues (Asp7, Thr11, Asp14, Asp14, and Thr 15) lying in one side of the helix, which provide a basis for the formation of water-filled channel architectures through self-associations. The significant broadening of the resonances of the hydrophilic residues Asp7, Thr11, and Asp14, which are buried inside SDS micelles, upon addition of Mn 2+ further verified the possibility of the formation of a channel through which metal ions pass. The substitution of Gly7 by an aspartate residue neither significantly altered the structure and membrane location of the peptide nor abolished its properties of channel forming and metal permeation compared with the wild-type peptide. © 2005 Wiley Periodicals, Inc.en_HK
dc.format.extent883807 bytes-
dc.format.extent254114 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypeapplication/pdf-
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.wiley.com/journalsen_HK
dc.relation.ispartofBiopolymersen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsBiopolymers. Copyright © John Wiley & Sons, Inc.en_HK
dc.subjectCD, DMT1en_HK
dc.subjectMicelleen_HK
dc.subjectNMRen_HK
dc.subjectTransmembrane peptideen_HK
dc.titleNMR structures and orientation of the fourth transmembrane domain of the rat divalent metal transporter (DMT1) with G185D mutation in SDS micellesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-3525&volume=77&issue=4&spage=173&epage=183&date=2005&atitle=NMR+structures+and+orientation+of+the+fourth+transmembrane+domain+of+the+rat+divalent+metal+transporter+(DMT1)+with+G185D+mutation+in+SDS+micellesen_HK
dc.identifier.emailSun, H:hsun@hkucc.hku.hken_HK
dc.identifier.authoritySun, H=rp00777en_HK
dc.description.naturepostprinten_HK
dc.identifier.doi10.1002/bip.20204en_HK
dc.identifier.pmid15660380-
dc.identifier.scopuseid_2-s2.0-15944397322en_HK
dc.identifier.hkuros98467-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-15944397322&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume77en_HK
dc.identifier.issue4en_HK
dc.identifier.spage173en_HK
dc.identifier.epage183en_HK
dc.identifier.isiWOS:000227248900001-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, H=37063577200en_HK
dc.identifier.scopusauthoridLi, F=36079222200en_HK
dc.identifier.scopusauthoridKwan, M=35187349100en_HK
dc.identifier.scopusauthoridHe, QY=34770287900en_HK
dc.identifier.scopusauthoridSun, H=7404827446en_HK
dc.identifier.citeulike3814102-

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