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Author Ryu, Jae Ha ♦ Jung, Hoi Jong ♦ Konishi, Shiro ♦ Kim, Ha Hyung ♦ Park, Zee-Yong ♦ Kim, Jae Il
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ MATHEMATICAL SOLUTIONS ♦ MEMBRANES ♦ NITROGEN 15 ♦ NUCLEAR MAGNETIC RESONANCE ♦ STRUCTURE-ACTIVITY RELATIONSHIPS ♦ TOXINS
Abstract To analyze structural features of ω-Aga IVA, a gating modifier toxin from spider venom, we here investigated the NMR solution structure of ω-Aga IVA within DPC micelles. Under those conditions, the Cys-rich central region of ω-Aga IVA still retains the inhibitor Cys knot motif with three short antiparallel β-strands seen in water. However, {sup 15}N HSQC spectra of ω-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 ω-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 ω-Aga IVA analogs indicate that both the hydrophobic C-terminal tail and an Arg patch in the core region of ω-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. - Highlights: • The NMR structure of ω-Aga IVA in DPC micelles is determined. • ω-Aga IVA stabilized its C-terminal tail with a β-turn structure within micelles. • Both the C-terminal tail and Arg patch play a crucial role for blocking Cav2.1.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2017-01-01
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 482
Issue Number 1


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