7CFT: Acid-sensing ion channel 1

Cryo-EM strucutre of human acid-sensing ion channel 1a in complex with snake toxin Mambalgin1 at pH 8.0. Determined by electron microscopy at 3.9 Å resolution. Released 21 Oct 2020.

Method: Electron microscopy
Resolution: 3.9 Å
Organisms: Homo sapiens, Dendroaspis polylepis polylepis
Chains: 6
Atoms: 11,283
Mol. weight: 185.16 kDa
Ligands: NAG
Released: 21 Oct 2020

Explore 7CFT in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7CFT contains 68 α-helices and 72 β-strands across 6 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chains A and B: 23 helices, 20 β-strands

Element	Residues	Length	Sheet
α-helix	50-66	17
β-strand	73-77	5	1
β-strand	85-86	2	2
α-helix	87-88	2
β-strand	89-94	6	3
α-helix	100-102	3
α-helix	105-110	6
α-helix	133-140	8
α-helix	154-160	7
α-helix	165-168	4
β-strand	173-174	2	4
β-strand	177-178	2	4
α-helix	181-183	3
β-strand	184	1	5
β-strand	187-189	3	3
β-strand	192-196	5	3
β-strand	197	1	5
α-helix	204-207	4
β-strand	208-209	2	2
β-strand	218	1	4
β-strand	220-222	3	6
α-helix	226-228	3
α-helix	230-231	2
β-strand	245-250	6	3
α-helix	255-256	2
α-helix	258-261	4
β-strand	263-265	3	3
β-strand	269-277	9	6
β-strand	278-281	4	1
α-helix	307-323	17
α-helix	335-338	4
α-helix	339-341	3
α-helix	342-346	5
α-helix	347-351	5
β-strand	372-375	4	6
β-strand	378-380	3	6
α-helix	387-393	7
β-strand	406-412	7	6
β-strand	418-424	7	1
α-helix	428-430	3
α-helix	431-439	9
α-helix	448-456	9
α-helix	458-461	4

Chain C: 22 helices, 20 β-strands

Element	Residues	Length	Sheet
α-helix	50-66	17
β-strand	73-77	5	13
β-strand	85-86	2	14
α-helix	87-88	2
β-strand	89-94	6	15
α-helix	105-110	6
α-helix	133-140	8
α-helix	154-160	7
α-helix	165-168	4
β-strand	173-174	2	16
β-strand	177-178	2	16
α-helix	181-183	3
β-strand	184	1	17
β-strand	187-189	3	15
β-strand	192-196	5	15
β-strand	197	1	17
α-helix	204-207	4
β-strand	208-209	2	14
β-strand	218	1	16
β-strand	220-222	3	18
α-helix	226-228	3
α-helix	230-231	2
β-strand	245-250	6	15
α-helix	255-256	2
α-helix	258-261	4
β-strand	263-265	3	15
β-strand	269-277	9	18
β-strand	278-281	4	13
α-helix	307-323	17
α-helix	335-338	4
α-helix	339-341	3
α-helix	342-346	5
α-helix	347-351	5
β-strand	372-375	4	18
β-strand	378-380	3	18
α-helix	387-393	7
β-strand	406-412	7	18
β-strand	418-424	7	13
α-helix	428-430	3
α-helix	431-439	9
α-helix	448-456	9
α-helix	458-461	4

Chains D, E and F: 0 helices, 4 β-strands

Element	Residues	Length	Sheet
β-strand	4	1	19
β-strand	9	1	19
β-strand	20-22	3	20
β-strand	34-36	3	20

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Acid-sensing ion channel 1	A, B, C	protein	477	Homo sapiens	P78348 (AlphaFold model)
Mambalgin-1	D, E, F	protein	57	Dendroaspis polylepis polylepis	P0DKR6 (AlphaFold model)

Sequence of entity 1 (A, B, C), FASTA

>7CFT_1 Acid-sensing ion channel 1 (chains A, B, C)
MHHHHHHHHMELKAEEEEVGGVQPVSIQAFASSSTLHGLAHIFSYERLSLKRALWALCFL
GSLAVLLCVCTERVQYYFHYHHVTKLDEVAASQLTFPAVTLCNLNEFRFSQVSKNDLYHA
GELLALLNNRYEIPDTQMADEKQLEILQDKANFRSFKPKPFNMREFYDRAGHDIRDMLLS
CHFRGEVCSAEDFKVVFTRYGKCYTFNSGRDGRPRLKTMKGGTGNGLEIMLDIQQDEYLP
VWGETDETSFEAGIKVQIHSQDEPPFIDQLGFGVAPGFQTFVACQEQRLIYLPPPWGTCK
AVTMDSDLDFFDSYSITACRIDCETRYLVENCNCRMVHMPGDAPYCTPEQYKECADPALD
FLVEKDQEYCVCEMPCNLTRYGKELSMVKIPSKASAKYLAKKFNKSEQYIGENILVLDIF
FEVLNYETIEQKKAYEIAGLLGDIGGQMGLFIGASILTVLELFDYAYEVIKHKLCRR

Sequence of entity 2 (D, E, F), FASTA

>7CFT_2 Mambalgin-1 (chains D, E, F)
LKCYQHGKVVTCHRDMKFCYHNTGMPFRNLKLILQGCSSSCSETENNKCCSTDRCNK

Ligands and cofactors

ID	Name	Formula	Copies
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	6

Primary citation

Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1. Sun, D., Liu, S., Li, S. et al. Elife (2020) 9. DOI 10.7554/eLife.57096 · PubMed

Other PDB entries of the same protein (UniProt P78348 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9E4I 2.33 Å, Human ASIC1a at pH 7.5 in complex with MitTx
9E4H 2.61 Å, Human ASIC1a at pH 5.7 with rotated, domain-swapped transmembrane domain
9E4F 2.69 Å, Human ASIC1a at pH 5.7 with domain-swapped transmembrane domain
9E4A 2.74 Å, Human ASIC1a at pH 8.5 with domain-swapped transmembrane domain
9E4K 2.77 Å, Human ASIC1a at pH 8.5, T26V mutation
9E4G 2.8 Å, Human ASIC1a at pH 5.7 with linear transmembrane domain
6L6N 2.86 Å, hASIC1a co-crystallized with Nafamostat
7RNN 2.86 Å, Human ASIC1a-Nb.C1 complex
9E4J 2.87 Å, Human ASIC1a at pH 6.5 in complex with MitTx
9E4B 3.09 Å, Human ASIC1a at pH 7.5 with domain-swapped transmembrane domain
9E4E 3.16 Å, Human ASIC1a at pH 6.5 with linear transmembrane domain
9E4D 3.19 Å, Human ASIC1a at pH 7.5 with linear transmembrane domain

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