Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5505728 | Biochemical and Biophysical Research Communications | 2017 | 6 Pages |
Abstract
To analyze structural features of Ï-Aga IVA, a gating modifier toxin from spider venom, we here investigated the NMR solution structure of Ï-Aga IVA within DPC micelles. Under those conditions, the Cys-rich central region of Ï-Aga IVA still retains the inhibitor Cys knot motif with three short antiparallel β-strands seen in water. However, 15N HSQC spectra of Ï-Aga IVA within micelles revealed that there are radical changes to the toxin's C-terminal tail and several loops upon binding to micelles. The C-terminal tail of Ï-Aga IVA appears to assume a β-turn like conformation within micelles, though it is disordered in water. Whole-cell patch clamp studies with several Ï-Aga IVA analogs indicate that both the hydrophobic C-terminal tail and an Arg patch in the core region of Ï-Aga IVA are critical for Cav2.1 blockade. These results suggest that the membrane environment stabilizes the structure of the toxin, enabling it to act in a manner similar to other gating modifier toxins, though its mode of interaction with the membrane and the channel is unique.
Keywords
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Jae Ha Ryu, Hoi Jong Jung, Shiro Konishi, Ha Hyung Kim, Zee-Yong Park, Jae Il Kim,