8DO3: Human Sec61 complex inhibited by eeyarestatin I

Cryo-EM structure of the human Sec61 complex inhibited by eeyarestatin I. Determined by electron microscopy at 3.22 Å resolution. Released 24 May 2023.

Method: Electron microscopy
Resolution: 3.22 Å
Organism: Homo sapiens
Chains: 3
Atoms: 4,185
Mol. weight: 70.57 kDa
Ligands: SWR
Released: 24 May 2023

Explore 8DO3 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8DO3 contains 29 α-helices and 11 β-strands across 3 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.

Chain A: 26 helices, 10 β-strands

Element	Residues	Length	Sheet
α-helix	9-13	5
β-strand	18-19	2	1
α-helix	20-22	3
α-helix	25-27	3
α-helix	28-46	19
β-strand	49	1	2
α-helix	50	1
β-strand	75	1	2
α-helix	76-78	3
α-helix	82-96	15
α-helix	107-133	27
α-helix	140-143	4
α-helix	145-168	24
α-helix	169-173	5
α-helix	178-196	19
β-strand	200-202	3	3
β-strand	207-209	3	3
α-helix	212-222	11
α-helix	228-234	7
α-helix	242-259	18
β-strand	262-269	8	4
β-strand	277-282	6	4
α-helix	289-311	23
α-helix	316-321	6
β-strand	323-324	2	5
β-strand	337-339	3	5
α-helix	341-344	4
α-helix	347-348	2
α-helix	351-356	6
α-helix	358-383	26
α-helix	387-397	11
β-strand	399-401	3	4
α-helix	406-409	4
α-helix	410-414	5
α-helix	417-438	22
α-helix	443-467	25

Chain B: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	8-24	17
α-helix	30-65	36

Chain C: 1 helix, 1 β-strand

Element	Residues	Length	Sheet
β-strand	67-68	2	1
α-helix	70-94	25

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Protein transport protein Sec61 subunit gamma	B	protein	68	Homo sapiens	P60059 (AlphaFold model)
Protein transport protein Sec61 subunit beta	C	protein	96	Homo sapiens	P60468 (AlphaFold model)
Protein transport protein Sec61 subunit alpha isoform 1	A	protein	476	Homo sapiens	P61619 (AlphaFold model)

Sequence of entity 1 (B), FASTA

>8DO3_1 Protein transport protein Sec61 subunit gamma (chains B)
MDQVMQFVEPSRQFVKDSIRLVKRCTKPDRKEFQKIAMATAIGFAIMGFIGFFVKLIHIP
INNIIVGG

Sequence of entity 2 (C), FASTA

>8DO3_2 Protein transport protein Sec61 subunit beta (chains C)
MPGPTPSGTNVGSSGRSPSKAVAARAAGSTVRQRKNASCGTRSAGRTTSAGTGGMWRFYT
EDSPGLKVGPVPVLVMSLLFIASVFMLHIWGKYTRS

Sequence of entity 3 (A), FASTA

>8DO3_3 Protein transport protein Sec61 subunit alpha isoform 1 (chains A)
MAIKFLEVIKPFCVILPEIQKPERKIQFKEKVLWTAITLFIFLVCCQIPLFGIMSSDSAD
PFYWMRVILASNRGTLMELGISPIVTSGLIMQLLAGAKIIEVGDTPKDRALFNGAQKLFG
MIITIGQSIVYVMTGMYGDPSEMGAGICLLITIQLFVAGLIVLLLDELLQKGYGLGSGIS
LFIATNICETIVWKAFSPTTVNTGRGMEFEGAIIALFHLLATRTDKVRALREAFYRQNLP
NLMNLIATIFVFAVVIYFQGFRYELPIRSTKVRGQIGIYPIKLFYTSNIPIILQSALVSN
LYVISQMLSARFSGNLLVSLLGTWSDTSSGGPARAYPVGGLCYYLSPPESFGSVLEDPVH
AVVYIVFMLGSCAFFSKTWIEVSGSSPRDIAKQFKDQGMVINGKRETSIYRELKKIIPTA
AAFGGLCIGALSVLADFLGAIGSGTGILLAVTIIYQYFEIFVKEQSEVGSMGALLF

Ligands and cofactors

ID	Name	Formula	Copies
SWR	N'-(4-chlorophenyl)-N-[(4R)-3-(4-chlorophenyl)-5,5-dimethyl-1-(2-{(2E)-2-[(2E)-…	C27 H25 Cl2 N7 O7	1

Primary citation

A common mechanism of Sec61 translocon inhibition by small molecules. Itskanov, S., Wang, L., Junne, T. et al. Nat Chem Biol (2023) 19:1063-1071. DOI 10.1038/s41589-023-01337-y · PubMed

Other PDB entries of the same protein (UniProt P60059 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8DNZ 2.57 Å, Cryo-EM structure of the human Sec61 complex inhibited by apratoxin F
8DNY 2.85 Å, Cryo-EM structure of the human Sec61 complex inhibited by decatransin
8DO0 2.86 Å, Cryo-EM structure of the human Sec61 complex inhibited by mycolactone
8DO2 2.95 Å, Cryo-EM structure of the human Sec61 complex inhibited by cyclotriazadisulfonamide (CADA)
8DNX 2.98 Å, Cryo-EM structure of the human Sec61 complex inhibited by cotransin
8DO1 3.01 Å, Cryo-EM structure of the human Sec61 complex inhibited by ipomoeassin F
8DNV 3.03 Å, Cryo-EM structure of the human Sec61 complex in a partially-open apo state (Class 1)
9D6L 3.1 Å, Human Sec61 complex inhibited by KZR-261
9YWS 3.1 Å, Human Sec61 complex bound to coibamide A
9N9J 3.2 Å, Structure of a GRP94 folding intermediate engaged with a CCDC134- and FKBP11-bound…
8OJ0 3.3 Å, 60S ribosomal subunit bound to the E3-UFM1 complex - state 2 (native)
8OJ8 3.3 Å, 60S ribosomal subunit bound to the E3-UFM1 complex - state 1 (native)

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