Homology-guided mutational analysis reveals the functional requirements for antinociceptive specificity of collapsin response mediator protein 2-derived peptides.

ABSTRACT:

Background and purpose

N-type voltage-gated calcium (Ca_v 2.2) channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Although Ca_v 2.2 channel antagonists are recommended as first-line treatment for neuropathic pain, calcium-current blocking gabapentinoids inadequately alleviate chronic pain symptoms and often exhibit numerous side effects. Collapsin response mediator protein 2 (CRMP2) targets Ca_v 2.2 channels to the sensory neuron membrane and allosterically modulates their function. A 15-amino-acid peptide (CBD3), derived from CRMP2, disrupts the functional protein-protein interaction between CRMP2 and Ca_v 2.2 channels to inhibit calcium influx, transmitter re

SUBMITTER: Moutal A 

PROVIDER: S-EPMC5980424 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature