The author list originally given in Wang et al. Chin. Phys. B 31 108702 (2022) has been amended to remove four authors, Hua Li, Bin Wu, Jun Guo and Chenqi Xu, who believe their contributions are more suitable to be cr...The author list originally given in Wang et al. Chin. Phys. B 31 108702 (2022) has been amended to remove four authors, Hua Li, Bin Wu, Jun Guo and Chenqi Xu, who believe their contributions are more suitable to be credited in the acknowledgments.展开更多
Copper ions can promote amyloid diseases that are associated with amyloid peptides, such as type 2 diabetes(T2D),Alzheimer's disease(AD), Parkinson's disease(PD), and amyotrophic lateral sclerosis(ALS). Howeve...Copper ions can promote amyloid diseases that are associated with amyloid peptides, such as type 2 diabetes(T2D),Alzheimer's disease(AD), Parkinson's disease(PD), and amyotrophic lateral sclerosis(ALS). However, the underlying molecular mechanism remains obscure. Here we present that Cu^(2+)is able to specifically bind to the backbone of T2D related human islet amyloid polypeptide(hIAPP) by forming a ring structure, which causes the reduction of Cu^(2+)to Cu^(+) to produce reactive oxygen species(ROS) and the modulation of hIAPP aggregation. Nuclear magnetic resonance spectroscopy showed that Cu^(2+)bound to the backbone of a turn region, His18-Ser21, which is critical for hIAPP aggregation.Ab initio calculations and x-ray absorption fine structure analyses revealed that Cu^(2+)simultaneously bound with both the amide nitrogen and carbonyl oxygen on the peptide backbone, resulting in a ring structure, and causing the reduction of Cu^(2+)to Cu^(+) to form a hIAPP-Cu^(+) complex. 2′,7′-dichlorodihydrofluorescin diacetate fluorescence measurements further indicated that this complex led to enhanced ROS levels in rat insulinoma cells. Additionally, thioflavin T fluorescence and atomic force microscopy measurements denoted that the backbone-Cu ring structure largely modulated hIAPP aggregation,including the inhibition of hIAPP fibrillation and the promotion of peptide oligomerization. These findings shed new light on the molecular mechanism of Cu^(2+)-induced amyloid toxicity involving both the enhancement of ROS and the modulation of hIAPP aggregation.展开更多
Metallomics is proposed as a new omics to fol- low genomics, proteomics and metabolomics. This paper gives an overview of the development of met- allomics based on the introduction of the concept of metallomics and it...Metallomics is proposed as a new omics to fol- low genomics, proteomics and metabolomics. This paper gives an overview of the development of met- allomics based on the introduction of the concept of metallomics and its methodology.展开更多
文摘The author list originally given in Wang et al. Chin. Phys. B 31 108702 (2022) has been amended to remove four authors, Hua Li, Bin Wu, Jun Guo and Chenqi Xu, who believe their contributions are more suitable to be credited in the acknowledgments.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 12074208 and 11375256)the Natural Science Foundation of Jiangsu Province (Grant No. BK20200176)+2 种基金the Natural Science Foundation of Jiangsu Higher Education Institutions of China (Grant Nos. 20KJB140020 and 19KJB140005)Fundamental Research Project from Changzhou Science and Technology (Grant No. CJ20200029)the Jiangsu Province High-level Innovative and Entrepreneurial Talents Introduction Plan。
文摘Copper ions can promote amyloid diseases that are associated with amyloid peptides, such as type 2 diabetes(T2D),Alzheimer's disease(AD), Parkinson's disease(PD), and amyotrophic lateral sclerosis(ALS). However, the underlying molecular mechanism remains obscure. Here we present that Cu^(2+)is able to specifically bind to the backbone of T2D related human islet amyloid polypeptide(hIAPP) by forming a ring structure, which causes the reduction of Cu^(2+)to Cu^(+) to produce reactive oxygen species(ROS) and the modulation of hIAPP aggregation. Nuclear magnetic resonance spectroscopy showed that Cu^(2+)bound to the backbone of a turn region, His18-Ser21, which is critical for hIAPP aggregation.Ab initio calculations and x-ray absorption fine structure analyses revealed that Cu^(2+)simultaneously bound with both the amide nitrogen and carbonyl oxygen on the peptide backbone, resulting in a ring structure, and causing the reduction of Cu^(2+)to Cu^(+) to form a hIAPP-Cu^(+) complex. 2′,7′-dichlorodihydrofluorescin diacetate fluorescence measurements further indicated that this complex led to enhanced ROS levels in rat insulinoma cells. Additionally, thioflavin T fluorescence and atomic force microscopy measurements denoted that the backbone-Cu ring structure largely modulated hIAPP aggregation,including the inhibition of hIAPP fibrillation and the promotion of peptide oligomerization. These findings shed new light on the molecular mechanism of Cu^(2+)-induced amyloid toxicity involving both the enhancement of ROS and the modulation of hIAPP aggregation.
基金supported by the National Basic Research Program of China(2003CB4 15001)the National Natural Science Foundation of China(20205008,20477053),
文摘Metallomics is proposed as a new omics to fol- low genomics, proteomics and metabolomics. This paper gives an overview of the development of met- allomics based on the introduction of the concept of metallomics and its methodology.