TAILIEUCHUNG - Báo cáo khoa học: Neuronal growth-inhibitory factor (metallothionein-3): structure–function relationships

Neuronal growth-inhibitory factor (GIF), also named metallothionein-3, inhibits the outgrowth of neuronal cells. Recent studies on the structure of human GIF, carried out using NMR and molecular dynamics simulation techniques, have been summarized. | ễFEBS Journal MINIREVIEW Neuronal growth-inhibitory factor metallothionein-3 structure-function relationships Zhi-Chun Ding Feng-Yun Ni1 and Zhong-Xian Huang ChemicalBiology Laboratory Department of Chemistry Fudan University Shanghai China Keywords metallothionein MT mutation neuronal growth-inhibitory factor GIF structurefunction relationship Correspondence . Huang ChemicalBiology Laboratory Department of Chemistry Fudan University Shanghai 200433 China Fax 86 21 65641740 Tel. 86 21 65643973 E-mail zxhuang@ Present address Immunology Immunotherapy Program Cancer Center Medical College of Georgia Augusta GA 30909 USA Department of Bioengineering Rice University Houston TX 77005 USA Received 5 January 2010 revised 5 March 2010 accepted 18 March 2010 Neuronal growth-inhibitory factor GIF also named metallothionein-3 inhibits the outgrowth of neuronal cells. Recent studies on the structure of human GIF carried out using NMR and molecular dynamics simulation techniques have been summarized. By studying a series of protein-engineered mutants of GIF we showed that the bioactivity of GIF is modulated by multiple factors including the unique TCPCP motif-induced characteristic conformation the solvent accessibility and dynamics of the metal-thiolate cluster and the domain-domain interactions. doi Introduction Metallothioneins MTs first discovered in horse kidney in 1957 by Margoshes Vallee are a family of small 7 kDa cysteine-rich and metal-binding proteins 1 . In mammals four subfamily MTs . MT1 MT2 MT3 and MT4 have been identified 2 . MT1 and MT2 are ubiquitous isoforms found in most organs and play critical roles in essential metal homeostasis and heavy metal ions detoxification 3 . By contrast MT3 and MT4 are specifically expressed in the central nervous system and the stratified squamous epithelia respectively 2 . MT3 first isolated and identified as a neuronal growth-inhibitory factor GIF has a distinct biological .

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