7RNN

Human ASIC1a-Nb.C1 complex

Summary for 7RNN

• Entry DOI: 10.2210/pdb7rnn/pdb
• EMDB information: 24580
• Descriptor: Nanobodies Nb.C1, Acid-sensing ion channel 1, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: channel proton-gated nanobody, membrane protein
• Biological source: Vicugna pacos (Alpaca); More
• Total number of polymer chains: 2
• Total formula weight: 73205.93

Authors

Wu, Y.,Chen, Z.,Sigworth, F.J.,Canessa, C.M. (deposition date: 2021-07-29, release date: 2021-08-11, Last modification date: 2024-10-30)

Primary citation

Wu, Y.,Chen, Z.,Sigworth, F.J.,Canessa, C.M.
Structure and analysis of nanobody binding to the human ASIC1a ion channel.
Elife, 10:-, 2021

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 (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.

PubMed: 34319232
DOI: 10.7554/eLife.67115

Experimental method

ELECTRON MICROSCOPY (2.86 Å)