Solution structure of potassium channel-inhibiting scorpion toxin Lq2

Lq2 is a unique scorpion toxin, Acting from the extracellular side, Lq2 blo cks the ion conduction pore in not only the voltage- and Ca2+-activated cha nnels, but also the inward-rectifier K+ channels. This finding argues that the three-dimensional structures of the pores in these K+ channels are simi lar, However, the amino acid sequences that form the external part of the p ore are minimally conserved among the various classes of K+ channels. Becau se Lq2 can bind to all the three classes of K+ channels, we can use Lq2 as a structural probe to examine how the non-conserved pore-forming sequences are arranged in space to form similar pore structures, In the present study , we determined the three-dimensional structure of Lq2 using nuclear magnet ic resonance (NMR) techniques. Lq2 consists of an or-helix (residues S10 to L20) and a beta-sheet, connected by an alpha beta 3 loop (residues N22 to N24). The beta-sheet has two well-defined anti-parallel strands (residues G 26 to M29 and residues K32 to C35), which are connected by a type I' beta-t urn centered between residues N30 and K31. The N-terminal segment (residues Z1 to T8) appears to form a quasi-third strand of the beta-sheet. Proteins 1999;34:417-426. (C) 1999 Wiley-Liss, Inc.