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Structural basis for CaVα2δ:gabapentin binding
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DOI：10.1038/s41594-023-00951-7.png)
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Abstract
En 中文
Gabapentinoid drugs for pain and anxiety act on the Ca-V alpha(2)delta-1 and Ca-V alpha(2)delta-2 subunits of high-voltage-activated calcium channels (Ca(V)1s and Ca(V)2s). Here we present the cryo-EM structure of the gabapentin-bound brain and cardiac Ca(V)1.2/Ca-V beta(3)/Ca-V alpha(2)delta-1 channel. The data reveal a binding pocket in the Ca-V alpha(2)delta-1 dCache1 domain that completely encapsulates gabapentin and define Ca-V alpha(2)delta isoform sequence variations that explain the gabapentin binding selectivity of Ca-V alpha(2)delta-1 and Ca-V alpha(2)delta-2. Gabapentinoid drugs are widely used for pain, epilepsy and mental disorders. Chen et al. report the structure of a gabapentin-bound brain and heart calcium channel, revealing the gabapentin binding site and isoform-selective binding determinants.
Keywords:
GATED CALCIUM-CHANNELS
ALPHA(2)DELTA SUBUNITS
GABAPENTIN
PREGABALIN
TRAFFICKING
DRUG
PHARMACOLOGY
EXPRESSION
PHYSIOLOGY
PROTEINS
Journal
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IF:
10.1
Papers:
4.8K
Citations:
2.8W
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