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-Structure paper
Title | Structure and analysis of nanobody binding to the human ASIC1a ion channel. |
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Journal, issue, pages | Elife, Vol. 10, Year 2021 |
Publish date | Jul 28, 2021 |
Authors | Yangyu Wu / Zhuyuan Chen / Fred J Sigworth / Cecilia M Canessa / |
PubMed Abstract | ASIC1a is a proton-gated sodium channel involved in modulation of pain, fear, addiction, and ischemia-induced neuronal injury. We report isolation and characterization of alpaca-derived nanobodies ...ASIC1a is a proton-gated sodium channel involved in modulation of pain, fear, addiction, and ischemia-induced neuronal injury. We report isolation and characterization of alpaca-derived nanobodies (Nbs) that specifically target human ASIC1a. Cryo-electron microscopy of the human ASIC1a channel at pH 7.4 in complex with one of these, Nb.C1, yielded a structure at 2.9 Å resolution. It is revealed that Nb.C1 binds to a site overlapping with that of the Texas coral snake toxin (MitTx1) and the black mamba venom Mambalgin-1; however, the Nb.C1-binding site does not overlap with that of the inhibitory tarantula toxin psalmotoxin-1 (PcTx1). Fusion of Nb.C1 with PcTx1 in a single polypeptide markedly enhances the potency of PcTx1, whereas competition of Nb.C1 and MitTx1 for binding reduces channel activation by the toxin. Thus, Nb.C1 is a molecular tool for biochemical and structural studies of hASIC1a; a potential antidote to the pain-inducing component of coral snake bite; and a candidate to potentiate PcTx1-mediated inhibition of hASIC1a in vivo for therapeutic applications. |
External links | Elife / PubMed:34319232 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.86 Å |
Structure data | EMDB-24580, PDB-7rnn: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | MEMBRANE PROTEIN / Channel Proton-gated Nanobody |