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First, the high-resolution apo structure of TRPV1 was used on its own, and then the Kv 1.2/2.1 chimera structure was also included.
The K+ ions in the paddle chimera structure are shown in light blue and those in the toxin-channel complex in cyan.
A multitemplate combination consisting mostly of the apo TRPV1 structure, but including the linker region of the Kv channel chimera structure, was then devised.
However, some indication of possible hydrogen bonds with backbone carbonyls at this end of S6 was also seen, but only in initial models based on the Kv 1.2/2.1 chimera structure (Table S3 of the Supporting Information).
(A ) Shown is a stereoview of the bound CTX in surface rendition in the CTX paddle chimera structure from an intracellular perspective viewing down the fourfold symmetry axis of the channel (channel not shown).
(C ) Side view of the selectivity filter (two diagonal subunits, molecule B) from the paddle chimera structure shown in stick rendition with the K+ ions shown as cyan spheres.
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These viruses are assumed to have acquired distinctive properties conferred by the chimera structures that make them different from the original vaccine and challenge viruses.
Our first major finding is that we do not see discernible changes in the structure of the channel between the toxin-bound and the toxin-free paddle chimera structures.
Side chains constituting the aromatic cuff are highlighted in gray (see above) and all positions studied here are indicated using their numbering in Shaker potassium channels (these residues correspond to Trp362, Trp363, Ser367, Thr369, Thr370, Tyr373 and Asp375 in the Kv1.2/Kv2.1 [voltage-gated potassium channel isoforms 1.2 and 2.1] chimera crystal structure [ PDB 2R9R ]).
Mutant DDX3X structures were generated in Chimera and each structure was minimized.
Note that the position equivalent to position 439 in Shaker (Thr439) is a serine in the Kv1.2/2.1 chimera; (B ) Chemical structures of side chains at position 435 and representative currents for Trp435 (WT), Trp435Tyr and Trp435Phe (−80 mV to +20 mV, 10 mV increments).
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