Solution structure and dynamics of human metallothionein-3 (MT-3).
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 alpha-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 (beta-domain) and one in the C-terminus (alpha-domain). The overall fold of the alpha-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 beta-domain exhibits similar internal motion to the alpha-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.
Wang
Hui
H
Department of Chemistry and Open Laboratory of Chemical Biology, The University of Hong Kong, Pokfulam Road, Hong Kong, PR China.
Zhang
Qi
Q
Cai
Bin
B
Li
Hongyan
H
Sze
Kong-Hung
KH
Huang
Zhong-Xian
ZX
Wu
Hou-Ming
HM
Sun
Hongzhe
H
D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002470:Cell Survival; D003712:Dendrites / Q000378:metabolism; D006801:Humans; D000090023:Metallothionein 3; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D000682:Amyloid; D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D009419:Nerve Tissue Proteins