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Solution structure and dynamics of human metallothionein‐3 (MT‐3)
Author(s) -
Wang Hui,
Zhang Qi,
Cai Bin,
Li Hongyan,
Sze Kong-Hung,
Huang Zhong-Xian,
Wu Hou-Ming,
Sun Hongzhe
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.12.099
Subject(s) - metallothionein , extracellular , human brain , chemistry , c terminus , biophysics , neurotrophic factors , amyloid (mycology) , neurite , microbiology and biotechnology , biochemistry , neuroscience , biology , amino acid , receptor , inorganic chemistry , gene , in vitro
Alzheimer's disease is characterized by progressive loss of neurons accompanied by the formation of intraneural neurofibrillary tangles and extracellular amyloid plaques. Human neuronal growth inhibitory factor, classified as metallothionein‐3 (MT‐3), was found to be related to the neurotrophic activity promoting cortical neuron survival and dendrite outgrowth in the cell culture studies. We have determined the solution structure of the α‐domain of human MT‐3 (residues 32–68) by multinuclear and multidimensional NMR spectroscopy in combination with the molecular dynamic simulated annealing approach. The human MT‐3 shows two metal–thiolate clusters, one in the N‐terminus (β‐domain) and one in the C‐terminus (α‐domain). The overall fold of the α‐domain is similar to that of mouse MT‐3. However, human MT‐3 has a longer loop in the acidic hexapeptide insertion than that of mouse MT‐3. Surprisingly, the backbone dynamics of the protein revealed that the β‐domain exhibits similar internal motion to the α‐domain, although the N‐terminal residues are more flexible. Our results may provide useful information for understanding the structure–function relationship of human MT‐3.