Idioma:

Important roles of the conserved linker-KKS in human neuronal growth inhibitory factor

Ding, Zhi-Chun ; Teng, Xin-Chen ; Zheng, Qi ; Ni, Feng-Yun ; Cai, Bin ; Wang, Yang ; Zhou, Guo-Ming ; Sun, Hong-Zhe ; Tan, Xiang-Shi ; Huang, Zhong-Xian

Biometals, 2009-10, Vol.22 (5), p.817-826 [Periódico revisado por pares]

Dordrecht: Dordrecht : Springer Netherlands

Texto completo disponível

Citações Citado por

Enviar para

Título:
Important roles of the conserved linker-KKS in human neuronal growth inhibitory factor
Autor: Ding, Zhi-Chun ; Teng, Xin-Chen ; Zheng, Qi ; Ni, Feng-Yun ; Cai, Bin ; Wang, Yang ; Zhou, Guo-Ming ; Sun, Hong-Zhe ; Tan, Xiang-Shi ; Huang, Zhong-Xian
Assuntos: Amino Acid Sequence ; Animals ; Biochemistry ; Biomedical and Life Sciences ; Cell Biology ; Cell culture ; Cerebral Cortex - cytology ; Cerebral Cortex - metabolism ; Humans ; Hydrogen-Ion Concentration ; Life Sciences ; Male ; Mass spectrometry ; Medicine/Public Health ; Metals ; Microbiology ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation ; Nerve Tissue Proteins - chemistry ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Neurology ; Neurons - cytology ; Neurons - metabolism ; Parkinson's disease ; Pharmacology/Toxicology ; Plant Physiology ; Protein Structure, Tertiary ; Rats ; Rats, Wistar ; Sequence Homology, Amino Acid
É parte de: Biometals, 2009-10, Vol.22 (5), p.817-826
Notas: http://dx.doi.org/10.1007/s10534-009-9228-1
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ObjectType-Article-2
ObjectType-Feature-1
Descrição: Metallothinein-3 (MT3), also named neuronal growth inhibitory factor (GIF), is attractive by its distinct neuronal growth inhibitory activity, which is not shared by other MT isoforms. The polypeptide chain of GIF is folded into two individual domains, which are connected by a highly conserved linker, KKS. In order to figure out the significance of the conserved segment, we constructed several mutants of human GIF (hGIF), including the K31/32A mutant, the K31/32E mutant and the KKS-SP mutant by site-directed mutagenesis. pH titration and DTNB reaction exhibited that all the three mutations made the β-domain lower in stability and looser. More significantly, change of KKS to SP also altered the general backbone conformation and metal-thiolate cluster geometry. Notably, bioassay results showed that the bioactivity of the K31/32A mutant and the K31/32E mutant decreased obviously, while the KKS-SP mutant lost inhibitory activity completely. Based on these results, we proposed that the KKS linker was a crucial factor in modulating the stability and the solvent accessibility of the Cd₃S₉ cluster in the β-domain through domain-domain interactions, thus was indispensable to the biological activity of hGIF.
Editor: Dordrecht: Dordrecht : Springer Netherlands
Idioma: Inglês;Holandês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

Important roles of the conserved linker-KKS in human neuronal growth inhibitory factor

Ding, Zhi-Chun ; Teng, Xin-Chen ; Zheng, Qi ; Ni, Feng-Yun ; Cai, Bin ; Wang, Yang ; Zhou, Guo-Ming ; Sun, Hong-Zhe ; Tan, Xiang-Shi ; Huang, Zhong-Xian

Dordrecht: Dordrecht : Springer Netherlands

Buscando em bases de dados remotas. Favor aguardar.