Open AccessStructures of pseudechetoxin and pseudecin, two snake‐venom cysteine‐rich secretory proteins that target cyclic nucleotide‐gated ion channels: implications for movement of the C‐terminal cysteine‐rich domain
Author(s) -
Suzuki Nobuhiro,
Yamazaki Yasuo,
Brown R. Lane,
Fujimoto Zui,
Morita Takashi,
Mizuno Hiroshi
Publication year - 2008
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s0907444908023512
Subject(s) - cyclic nucleotide gated ion channel , cysteine , cyclic nucleotide binding domain , ion channel , biophysics , chemistry , c terminus , biochemistry , ligand gated ion channel , amino acid , nucleotide , microbiology and biotechnology , biology , cyclic nucleotide , receptor , gene , enzyme
Cyclic nucleotide‐gated (CNG) ion channels play pivotal roles in sensory transduction by retinal photoreceptors and olfactory neurons. The elapid snake toxins pseudechetoxin (PsTx) and pseudecin (Pdc) are the only known protein blockers of CNG channels. These toxins belong to a cysteine‐rich secretory protein (CRISP) family containing an N‐terminal pathogenesis‐related proteins of group 1 (PR‐1) domain and a C‐terminal cysteine‐rich domain (CRD). PsTx and Pdc are highly homologous proteins, but their blocking affinities on CNG channels are different: PsTx blocks both the olfactory and retinal channels with ∼15–30‐fold higher affinity than Pdc. To gain further insights into their structure and function, the crystal structures of PsTx, Pdc and Zn 2+ ‐bound Pdc were determined. The structures revealed that most of the amino‐acid‐residue differences between PsTx and Pdc are located around the concave surface formed between the PR‐1 domain and the CRD, suggesting that the concave surface is functionally important for CNG‐channel binding and inhibition. A structural comparison in the presence and absence of Zn 2+ ion demonstrated that the concave surface can open and close owing to movement of the CRD upon Zn 2+ binding. The data suggest that PsTx and Pdc occlude the pore entrance and that the dynamic motion of the concave surface facilitates interaction with the CNG channels.