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TitleStructure and mechanism of a neuropeptide-activated channel in the ENaC/DEG superfamily.
Journal, issue, pagesNat Chem Biol, Vol. 19, Issue 10, Page 1276-1285, Year 2023
Publish dateAug 7, 2023
AuthorsFenglian Liu / Yu Dang / Lu Li / Hao Feng / Jianlin Li / Haowei Wang / Xu Zhang / Zhe Zhang / Sheng Ye / Yutao Tian / Qingfeng Chen /
PubMed AbstractPhe-Met-Arg-Phe-amide (FMRFamide)-activated sodium channels (FaNaCs) are a family of channels activated by the neuropeptide FMRFamide, and, to date, the underlying ligand gating mechanism remains ...Phe-Met-Arg-Phe-amide (FMRFamide)-activated sodium channels (FaNaCs) are a family of channels activated by the neuropeptide FMRFamide, and, to date, the underlying ligand gating mechanism remains unknown. Here we present the high-resolution cryo-electron microscopy structures of Aplysia californica FaNaC in both apo and FMRFamide-bound states. AcFaNaC forms a chalice-shaped trimer and possesses several notable features, including two FaNaC-specific insertion regions, a distinct finger domain and non-domain-swapped transmembrane helix 2 in the transmembrane domain (TMD). One FMRFamide binds to each subunit in a cleft located in the top-most region of the extracellular domain, with participation of residues from the neighboring subunit. Bound FMRFamide adopts an extended conformation. FMRFamide binds tightly to A. californica FaNaC in an N terminus-in manner, which causes collapse of the binding cleft and induces large local conformational rearrangements. Such conformational changes are propagated downward toward the TMD via the palm domain, possibly resulting in outward movement of the TMD and dilation of the ion conduction pore.
External linksNat Chem Biol / PubMed:37550431
MethodsEM (single particle)
Resolution2.9 - 3.0 Å
Structure data

34122

7yvb

EMDB-34122, PDB-7yvb:
Aplysia californica FaNaC in ligand bound state
Method: EM (single particle) / Resolution: 2.9 Å

34123

7yvc

EMDB-34123, PDB-7yvc:
Aplysia californica FaNaC in apo state
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-CA:
Unknown entry

Source
  • aplysia californica (California sea hare)
  • synthetic construct (others)
KeywordsTRANSPORT PROTEIN / neuropeptide / ion channel / FMRFamide

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