FIGURE 1.

Molecular docking of mambalgin-2 on the three-dimensional model structure of rat ASIC1a. A, surface representation of the ASIC1a·mambalgin-2 complex (side view in the top panel and top view in the bottom panel). Subunits are shown with different gray levels; toxins are shown in blue. The structure of mambalgin-2 (Mamb-2) alone is shown on the left with labeling of the different fingers (see Ref. 23 for further details on the structure). B, close view of the mambalgin-2 binding site at the interface between subunits A and B (a mapping of the region in a schematic of the trimeric channel is displayed at the bottom right). The toxin with its fingers I, II, and III is shown in blue ribbon. Domains in the ASIC1a extracellular loop are shown with different colors and refer to the domains identified by Jasti et al. (32) and listed in the inset. Transmembrane domains 1 and 2 are represented by only one red block (TM1+TM2). C, localization of the three domains potentially located at the interface with mambalgin-2 on a surface representation of a trimeric rat ASIC1a channel (side view). D and E, localization of the same domains on a schematic representation of the channel (D) and on a linear representation of an isolated subunit (E). F, protein sequence alignment of the rat ASIC1a and ASIC2a proteins (the N- and C-terminal cytoplasmic domains are not shown). Amino acids that are identical or similar are printed white on black or black on gray background, respectively. The two transmembrane domains (M1 and M2) as well as domains P, β, and T are indicated above the sequences. Key residues identified in this study for the mambalgin-2 effect are highlighted by red squares.