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Article: Structure and topology of the transmembrane domain 4 of the divalent metal transporter in membrane-mimetic environments

TitleStructure and topology of the transmembrane domain 4 of the divalent metal transporter in membrane-mimetic environments
Authors
KeywordsDMT1
Membrane
NMR
Structure
Issue Date2004
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/EJB
Citation
European Journal Of Biochemistry, 2004, v. 271 n. 10, p. 1938-1951 How to Cite?
AbstractThe divalent metal transporter (DMT1) is a 12-transmembrane domain protein responsible for dietary iron uptake in the duodenum and iron acquisition from transferrin in peripheral tissues. The transmembrane domain 4 (TM4) of DMT1 has been shown to be crucial for its biological function. Here we report the 3D structure and topology of the DMT1-TM4 peptide by NMR spectroscopy with simulated annealing calculations in membrane-mimetic environments, e.g. 2,2,2-trifluoroethanol and SDS micelles. The 3D structures of the peptide are similar in both environments, with nonordered and flexible N- and C-termini flanking an ordered helical region. The final set of the 16 lowest energy structures is particularly well defined in the region of residues Leu9-Phe20 in 2,2,2-trifluoroethanol, with a mean pairwise root mean square deviation of 0.23 ± 0.10 Å for the backbone heavy atoms and 0.82 ± 0.17 Å for all heavy atoms. In SDS micelles, the length of the helix is dependent on pH values. In particular, the C-terminus becomes well-structured at low pH (4.0), whereas the N-terminal segment (Arg1-Gly7) is flexible and poorly defined at all pH values studied. The effects of 12-doxylPtdCho spin-label and paramagnetic metal ions on NMR signal intensities demonstrated that both the N-terminus and helical region of the TM4 are embedded into the interior of SDS micelles. Unexpectedly, we observed that amide protons exchanged much faster in SDS than in 2,2, 2-trifluoroethanol, indicating that there is possible solvent accessibility in the structure. The paramagnetic metal ions broaden NMR signals from residues both situated in aqueous phase and in the helical region. From these results we speculate that DMT1-TM4s may self-assemble to form a channel through which metal ions are likely to be transported. These results might provide an insight into the structure-function relationship for the integral DMT1.
Persistent Identifierhttp://hdl.handle.net/10722/69200
ISSN
2006 Impact Factor: 3.579
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, Hen_HK
dc.contributor.authorLi, Fen_HK
dc.contributor.authorQian, ZWen_HK
dc.contributor.authorSun, Hen_HK
dc.date.accessioned2010-09-06T06:11:29Z-
dc.date.available2010-09-06T06:11:29Z-
dc.date.issued2004en_HK
dc.identifier.citationEuropean Journal Of Biochemistry, 2004, v. 271 n. 10, p. 1938-1951en_HK
dc.identifier.issn0014-2956en_HK
dc.identifier.urihttp://hdl.handle.net/10722/69200-
dc.description.abstractThe divalent metal transporter (DMT1) is a 12-transmembrane domain protein responsible for dietary iron uptake in the duodenum and iron acquisition from transferrin in peripheral tissues. The transmembrane domain 4 (TM4) of DMT1 has been shown to be crucial for its biological function. Here we report the 3D structure and topology of the DMT1-TM4 peptide by NMR spectroscopy with simulated annealing calculations in membrane-mimetic environments, e.g. 2,2,2-trifluoroethanol and SDS micelles. The 3D structures of the peptide are similar in both environments, with nonordered and flexible N- and C-termini flanking an ordered helical region. The final set of the 16 lowest energy structures is particularly well defined in the region of residues Leu9-Phe20 in 2,2,2-trifluoroethanol, with a mean pairwise root mean square deviation of 0.23 ± 0.10 Å for the backbone heavy atoms and 0.82 ± 0.17 Å for all heavy atoms. In SDS micelles, the length of the helix is dependent on pH values. In particular, the C-terminus becomes well-structured at low pH (4.0), whereas the N-terminal segment (Arg1-Gly7) is flexible and poorly defined at all pH values studied. The effects of 12-doxylPtdCho spin-label and paramagnetic metal ions on NMR signal intensities demonstrated that both the N-terminus and helical region of the TM4 are embedded into the interior of SDS micelles. Unexpectedly, we observed that amide protons exchanged much faster in SDS than in 2,2, 2-trifluoroethanol, indicating that there is possible solvent accessibility in the structure. The paramagnetic metal ions broaden NMR signals from residues both situated in aqueous phase and in the helical region. From these results we speculate that DMT1-TM4s may self-assemble to form a channel through which metal ions are likely to be transported. These results might provide an insight into the structure-function relationship for the integral DMT1.en_HK
dc.languageengen_HK
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/EJBen_HK
dc.relation.ispartofEuropean Journal of Biochemistryen_HK
dc.rightsEuropean Journal of Biochemistry. Copyright © Blackwell Publishing Ltd.en_HK
dc.subjectDMT1en_HK
dc.subjectMembraneen_HK
dc.subjectNMRen_HK
dc.subjectStructureen_HK
dc.titleStructure and topology of the transmembrane domain 4 of the divalent metal transporter in membrane-mimetic environmentsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0014-2956&volume=271&spage=1938&epage=1951&date=2004&atitle=Structure+and+topology+of+the+transmembrane+domain+4+of+the+divalent+metal+transporter+in+membrane-mimetic+environmentsen_HK
dc.identifier.emailSun, H:hsun@hkucc.hku.hken_HK
dc.identifier.authoritySun, H=rp00777en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/j.1432-1033.2004.04104.xen_HK
dc.identifier.pmid15128303-
dc.identifier.scopuseid_2-s2.0-2442683958en_HK
dc.identifier.hkuros92346en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-2442683958&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume271en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1938en_HK
dc.identifier.epage1951en_HK
dc.identifier.isiWOS:000221135700014-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLi, H=14023043100en_HK
dc.identifier.scopusauthoridLi, F=36079222200en_HK
dc.identifier.scopusauthoridQian, ZW=36111653800en_HK
dc.identifier.scopusauthoridSun, H=7404827446en_HK
dc.identifier.citeulike3814142-

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