Abstract: Metal ions interact with protein using a great variety of mechanisms to regulate protein functions. Some metal ions bind tightly and specifically to proteins and markedly regulate protein function, while others interact loosely and nonspecifically with proteins and only act as cofactors for protein functioning. In this review, we describe nuclear magnetic resonance (NMR) techniques which are widely used to investigate inter-molecular interactions between proteins and diamagnetic/paramagnetic metal ions. Special emphasis is put on the NMR techniques the can be used to elucidate the structure and function of metalloproteins, including chemical shift mapping, paramagnetic NMR and backbone dynamics detection. Examples are given to illustrate how the NMR techniques can be used to map inter-molecular interaction between proteins (calmodulin, zinc fingers and prion proteins) and metal ions.

Key words: NMR, protein-metal ion interaction, chemical shift mapping, backbone dynamics, paramagnetic effect, 3D structure