Structural Elucidation of the Protein- and Membrane-Binding Properties of the N-Terminal Tail Domain of Human Annexin II

The conformational preferences and the solution structure of AnxII ^N31, a peptide corresponding to the full-length sequence (residues 1-31) of the human annexin II N-terminal tail domain, were investigated by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. CD results showed that AnxII^N31 adopts a mainly α-helical conformation in hydrophobic or membrane-mimetic environments, while a predominantly random structure is adopted in aqueous buffer. In contrast to previous results of the annexin I N-terminal domain peptide [Yoon et al. (2000) FEBS Lett. 484, 241-245], calcium ions showed no effect on the structure of AnxII^N31. The NMR-derived structure of AnxII^N31 in 50% TFE/water mixture showed a horseshoe-like fold comprising the N-terminal amphipathic α-helix, the following loop, and the C-terminal helical region. Together, the results establish the first detailed structural data on the N-terminal tail domain of annexin II, and suggest the possibility of the domain to undergo Ca²⁺-independent membrane-binding.