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.
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