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Article: Effect of α-domain substitution on the structure, property and function of human neuronal growth inhibitory factor

TitleEffect of α-domain substitution on the structure, property and function of human neuronal growth inhibitory factor
Authors
Issue Date2007
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00775/index.htm
Citation
Journal Of Biological Inorganic Chemistry, 2007, v. 12 n. 8, p. 1173-1179 How to Cite?
AbstractHuman metallothionein-3 (hMT3), also named human neuronal growth inhibitory factor (hGIF), is attractive due to its distinct neuronal growth inhibitory activity, which is not shown by other human MT isoforms. It has been reported that the neuronal growth inhibitory activity arises from the N-terminal β-domain rather than its C-terminal α-domain. However, previous bioassay results have shown that the single β-domain is less effective at inhibiting the neuron growth than that in intact hMT3 on a molar basis, which suggests that the α-domain is indispensable to the neuronal growth inhibitory activity of hMT3. In order to confirm this assumption, we constructed two domain-hybrid mutants, the β(MT3)-β(MT3) mutant and the β(MT3)-α(MT1) mutant, and investigated their structural and metal binding properties by UV-vis spectroscopy, CD spectroscopy, pH titration, DTNB reaction, EDTA reaction, etc. The results showed that stability of the Cd 3S 9 cluster of the β(MT3)-β(MT3) mutant decreased significantly while the Cd 3S 9 cluster of the β(MT3)-α(MT1) mutant had a similar stability and solvent accessibility to that of hMT3. Interestingly, the bioassay results showed that the neuronal growth inhibitory activity of the β(MT3)-β(MT3) mutant decreased significantly, while the β(MT3)-α(MT1) mutant showed similar inhibitory activity to hMT3. Based on these results, we conclude that the α-domain is indispensable and plays an important role in modulating the stability of the metal cluster in the β-domain by domain-domain interactions, thus influencing the bioactivity of hMT3. © 2007 SBIC.
Persistent Identifierhttp://hdl.handle.net/10722/168148
ISSN
2015 Impact Factor: 2.495
2015 SCImago Journal Rankings: 0.882
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorDing, ZCen_US
dc.contributor.authorZheng, Qen_US
dc.contributor.authorCai, Ben_US
dc.contributor.authorYu, WHen_US
dc.contributor.authorTeng, XCen_US
dc.contributor.authorWang, Yen_US
dc.contributor.authorZhou, GMen_US
dc.contributor.authorWu, HMen_US
dc.contributor.authorSun, HZen_US
dc.contributor.authorZhang, MJen_US
dc.contributor.authorHuang, ZXen_US
dc.date.accessioned2012-10-08T03:15:39Z-
dc.date.available2012-10-08T03:15:39Z-
dc.date.issued2007en_US
dc.identifier.citationJournal Of Biological Inorganic Chemistry, 2007, v. 12 n. 8, p. 1173-1179en_US
dc.identifier.issn0949-8257en_US
dc.identifier.urihttp://hdl.handle.net/10722/168148-
dc.description.abstractHuman metallothionein-3 (hMT3), also named human neuronal growth inhibitory factor (hGIF), is attractive due to its distinct neuronal growth inhibitory activity, which is not shown by other human MT isoforms. It has been reported that the neuronal growth inhibitory activity arises from the N-terminal β-domain rather than its C-terminal α-domain. However, previous bioassay results have shown that the single β-domain is less effective at inhibiting the neuron growth than that in intact hMT3 on a molar basis, which suggests that the α-domain is indispensable to the neuronal growth inhibitory activity of hMT3. In order to confirm this assumption, we constructed two domain-hybrid mutants, the β(MT3)-β(MT3) mutant and the β(MT3)-α(MT1) mutant, and investigated their structural and metal binding properties by UV-vis spectroscopy, CD spectroscopy, pH titration, DTNB reaction, EDTA reaction, etc. The results showed that stability of the Cd 3S 9 cluster of the β(MT3)-β(MT3) mutant decreased significantly while the Cd 3S 9 cluster of the β(MT3)-α(MT1) mutant had a similar stability and solvent accessibility to that of hMT3. Interestingly, the bioassay results showed that the neuronal growth inhibitory activity of the β(MT3)-β(MT3) mutant decreased significantly, while the β(MT3)-α(MT1) mutant showed similar inhibitory activity to hMT3. Based on these results, we conclude that the α-domain is indispensable and plays an important role in modulating the stability of the metal cluster in the β-domain by domain-domain interactions, thus influencing the bioactivity of hMT3. © 2007 SBIC.en_US
dc.languageengen_US
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00775/index.htmen_US
dc.relation.ispartofJournal of Biological Inorganic Chemistryen_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshHumansen_US
dc.subject.meshMetallothionein - Chemistry - Genetics - Metabolismen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutationen_US
dc.subject.meshNerve Tissue Proteins - Chemistry - Genetics - Metabolismen_US
dc.subject.meshNeurons - Drug Effectsen_US
dc.subject.meshProtein Structure, Tertiary - Geneticsen_US
dc.subject.meshRatsen_US
dc.subject.meshRecombinant Fusion Proteins - Chemistry - Genetics - Pharmacologyen_US
dc.titleEffect of α-domain substitution on the structure, property and function of human neuronal growth inhibitory factoren_US
dc.typeArticleen_US
dc.identifier.emailSun, HZ:hsun@hkucc.hku.hken_US
dc.identifier.authoritySun, HZ=rp00777en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1007/s00775-007-0287-xen_US
dc.identifier.pmid17712581-
dc.identifier.scopuseid_2-s2.0-35348921706en_US
dc.identifier.hkuros146185-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-35348921706&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume12en_US
dc.identifier.issue8en_US
dc.identifier.spage1173en_US
dc.identifier.epage1179en_US
dc.identifier.isiWOS:000250206100008-
dc.publisher.placeGermanyen_US
dc.identifier.scopusauthoridDing, ZC=14424225400en_US
dc.identifier.scopusauthoridZheng, Q=36887872800en_US
dc.identifier.scopusauthoridCai, B=36484162900en_US
dc.identifier.scopusauthoridYu, WH=55205334100en_US
dc.identifier.scopusauthoridTeng, XC=9842935500en_US
dc.identifier.scopusauthoridWang, Y=36078812500en_US
dc.identifier.scopusauthoridZhou, GM=8449295200en_US
dc.identifier.scopusauthoridWu, HM=13808047800en_US
dc.identifier.scopusauthoridSun, HZ=7404827446en_US
dc.identifier.scopusauthoridZhang, MJ=7601555100en_US
dc.identifier.scopusauthoridHuang, ZX=7406221847en_US

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