9PH4: COP9 signalosome
Cryo-EM structure of COP9 signalosome in complex with CSN5i-1a. Determined by electron microscopy at 3.0 Å resolution. Released 3 Dec 2025.
- Method
- Electron microscopy
- Resolution
- 3.0 Å
- Organism
- Homo sapiens
- Chains
- 8
- Atoms
- 15,982
- Mol. weight
- 328.64 kDa
- Ligands
- ZN, A1CH3
- Released
- 3 Dec 2025
Explore 9PH4 in 3D
Show helices and sheets
RCSB PDB
PDBe
Secondary structure: helices and β-sheets
9PH4 contains 107 α-helices and 41 β-strands across 8 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: 11 helices, 6 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 245-259 | 15 | |
| α-helix | 263-271 | 9 | |
| β-strand | 280 | 1 | 1 |
| β-strand | 284 | 1 | 1 |
| α-helix | 286-300 | 15 | |
| α-helix | 303-306 | 4 | |
| α-helix | 307-311 | 5 | |
| α-helix | 316-322 | 7 | |
| α-helix | 324-334 | 11 | |
| α-helix | 338-352 | 15 | |
| α-helix | 359-378 | 20 | |
| β-strand | 381-383 | 3 | 2 |
| α-helix | 397-409 | 13 | |
| β-strand | 415-418 | 4 | 2 |
| β-strand | 423-426 | 4 | 2 |
| α-helix | 431-462 | 32 | |
| β-strand | 466 | 1 | 3 |
Chain B: 11 helices, 3 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 252-264 | 13 | |
| α-helix | 273-286 | 14 | |
| α-helix | 297-299 | 3 | |
| α-helix | 300-303 | 4 | |
| α-helix | 310-320 | 11 | |
| α-helix | 323-329 | 7 | |
| α-helix | 341-344 | 4 | |
| α-helix | 347-363 | 17 | |
| β-strand | 366-370 | 5 | 2 |
| α-helix | 371-378 | 8 | |
| α-helix | 382-394 | 13 | |
| β-strand | 400-403 | 4 | 2 |
| β-strand | 408-411 | 4 | 2 |
| α-helix | 419-440 | 22 | |
Chain C: 27 helices, 6 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 4-15 | 12 | |
| α-helix | 21-29 | 9 | |
| α-helix | 57-63 | 7 | |
| α-helix | 75-86 | 12 | |
| α-helix | 90-92 | 3 | |
| α-helix | 97-113 | 17 | |
| α-helix | 118-120 | 3 | |
| α-helix | 121-129 | 9 | |
| β-strand | 137-138 | 2 | 4 |
| α-helix | 141-151 | 11 | |
| α-helix | 159-162 | 4 | |
| α-helix | 165-166 | 2 | |
| β-strand | 168-169 | 2 | 4 |
| α-helix | 178-194 | 17 | |
| α-helix | 198-210 | 13 | |
| β-strand | 213 | 1 | 3 |
| α-helix | 218-234 | 17 | |
| α-helix | 238-242 | 5 | |
| α-helix | 247-248 | 2 | |
| α-helix | 249-253 | 5 | |
| α-helix | 254-256 | 3 | |
| α-helix | 259-268 | 10 | |
| α-helix | 272-281 | 10 | |
| α-helix | 283-288 | 6 | |
| α-helix | 295-310 | 16 | |
| β-strand | 314-318 | 5 | 2 |
| α-helix | 319-326 | 8 | |
| α-helix | 331-344 | 14 | |
| β-strand | 349-352 | 4 | 2 |
| β-strand | 357-360 | 4 | 2 |
| α-helix | 361-363 | 3 | |
| α-helix | 370-398 | 29 | |
| α-helix | 401-404 | 4 | |
Chain D: 13 helices, 3 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 185-197 | 13 | |
| α-helix | 201-212 | 12 | |
| α-helix | 220-230 | 11 | |
| α-helix | 231-233 | 3 | |
| α-helix | 241-250 | 10 | |
| α-helix | 253-257 | 5 | |
| α-helix | 261-268 | 8 | |
| α-helix | 275-283 | 9 | |
| α-helix | 299-312 | 14 | |
| β-strand | 316-320 | 5 | 2 |
| α-helix | 324-328 | 5 | |
| α-helix | 332-344 | 13 | |
| β-strand | 351-353 | 3 | 2 |
| β-strand | 358-360 | 3 | 2 |
| α-helix | 366-391 | 26 | |
| α-helix | 395-404 | 10 | |
Chain E: 15 helices, 7 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 27-29 | 3 | |
| α-helix | 33-42 | 10 | |
| α-helix | 44-46 | 3 | |
| β-strand | 54-58 | 5 | 5 |
| α-helix | 59-71 | 13 | |
| β-strand | 78-86 | 9 | 5 |
| β-strand | 89-97 | 9 | 5 |
| α-helix | 109-113 | 5 | |
| α-helix | 114-126 | 13 | |
| α-helix | 131 | 1 | |
| β-strand | 132-139 | 8 | 5 |
| α-helix | 149-161 | 13 | |
| β-strand | 166-170 | 5 | 5 |
| α-helix | 172-178 | 7 | |
| β-strand | 183-188 | 6 | 5 |
| α-helix | 211-217 | 7 | |
| α-helix | 218-220 | 3 | |
| β-strand | 221-229 | 9 | 5 |
| α-helix | 232-250 | 19 | |
| α-helix | 254-257 | 4 | |
| α-helix | 260-281 | 22 | |
| α-helix | 287-316 | 30 | |
Chain F: 8 helices, 10 β-strands
| Element | Residues | Length | Sheet |
|---|
| β-strand | 40-43 | 4 | 6 |
| α-helix | 45-62 | 18 | |
| β-strand | 69-77 | 9 | 6 |
| β-strand | 80-88 | 9 | 6 |
| β-strand | 91-94 | 4 | 7 |
| β-strand | 97-100 | 4 | 7 |
| α-helix | 102-115 | 14 | |
| β-strand | 120-127 | 8 | 6 |
| α-helix | 131-132 | 2 | |
| α-helix | 133-143 | 11 | |
| β-strand | 150-154 | 5 | 6 |
| β-strand | 166-174 | 9 | 6 |
| β-strand | 179-186 | 8 | 6 |
| β-strand | 188-190 | 3 | 6 |
| α-helix | 194-205 | 12 | |
| α-helix | 216-247 | 32 | |
| α-helix | 254-265 | 12 | |
| α-helix | 273-312 | 40 | |
Chain G: 12 helices, 3 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 12-17 | 6 | |
| α-helix | 25-36 | 12 | |
| α-helix | 44-47 | 4 | |
| α-helix | 50-53 | 4 | |
| α-helix | 54-56 | 3 | |
| α-helix | 61-72 | 12 | |
| α-helix | 75-79 | 5 | |
| α-helix | 86-89 | 4 | |
| α-helix | 90-107 | 18 | |
| β-strand | 110-112 | 3 | 2 |
| α-helix | 113-119 | 7 | |
| α-helix | 125-137 | 13 | |
| β-strand | 141-146 | 6 | 2 |
| β-strand | 151-157 | 7 | 2 |
| α-helix | 167-220 | 54 | |
Chain H: 10 helices, 3 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 12-26 | 15 | |
| α-helix | 34-46 | 13 | |
| α-helix | 50-59 | 10 | |
| α-helix | 62-67 | 6 | |
| α-helix | 70-82 | 13 | |
| α-helix | 86-93 | 8 | |
| α-helix | 103-124 | 22 | |
| β-strand | 125-127 | 3 | 2 |
| β-strand | 128-129 | 2 | 8 |
| α-helix | 130-137 | 8 | |
| α-helix | 141-147 | 7 | |
| β-strand | 161-162 | 2 | 8 |
| α-helix | 196-208 | 13 | |
Molecules and chains
| Molecule | Chains | Type | Length | Organism | UniProt |
|---|
| COP9 signalosome complex subunit 1 | A | protein | 491 | Homo sapiens | Q13098 (AlphaFold model) |
| COP9 signalosome complex subunit 2 | B | protein | 443 | Homo sapiens | P61201 (AlphaFold model) |
| COP9 signalosome complex subunit 3 | C | protein | 423 | Homo sapiens | Q9UNS2 (AlphaFold model) |
| COP9 signalosome complex subunit 4 | D | protein | 406 | Homo sapiens | Q9BT78 (AlphaFold model) |
| COP9 signalosome complex subunit 5 | E | protein | 334 | Homo sapiens | Q92905 |
| COP9 signalosome complex subunit 6 | F | protein | 327 | Homo sapiens | Q7L5N1 |
| COP9 signalosome complex subunit 7b | G | protein | 264 | Homo sapiens | Q9H9Q2 |
| COP9 signalosome complex subunit 8 | H | protein | 209 | Homo sapiens | Q99627 |
Sequence of entity 1 (A), FASTA
>9PH4_1 COP9 signalosome complex subunit 1 (chains A)
MPLPVQVFNLQGAVEPMQIDVDPQEDPQNAPDVNYVVENPSLDLEQYAASYSGLMRIERL
QFIADHCPTLRVEALKMALSFVQRTFNVDMYEEIHRKLSEATRSSLRELQNAPDAIPESG
VEPPALDTAWVEATRKKALLKLEKLDTDLKNYKGNSIKESIRRGHDDLGDHYLDCGDLSN
ALKCYSRARDYCTSAKHVINMCLNVIKVSVYLQNWSHVLSYVSKAESTPEIAEQRGERDS
QTQAILTKLKCAAGLAELAARKYKQAAKCLLLASFDHCDFPELLSPSNVAIYGGLCALAT
FDRQELQRNVISSSSFKLFLELEPQVRDIIFKFYESKYASCLKMLDEMKDNLLLDMYLAP
HVRTLYTQIRNRALIQYFSPYVSADMHRMAAAFNTTVAALEDELTQLILEGLISARVDSH
SKILYARDVDQRSTTFEKSLLMGKEFQRRAKAMMLRAAVLRNQIHVKSPPREGSQGELTP
ANSQSRMSTNM
Sequence of entity 2 (B), FASTA
>9PH4_2 COP9 signalosome complex subunit 2 (chains B)
MSDMEDDFMCDDEEDYDLEYSEDSNSEPNVDLENQYYNSKALKEDDPKAALSSFQKVLEL
EGEKGEWGFKALKQMIKINFKLTNFPEMMNRYKQLLTYIRSAVTRNYSEKSINSILDYIS
TSKQMDLLQEFYETTLEALKDAKNDRLWFKTNTKLGKLYLEREEYGKLQKILRQLHQSCQ
TDDGEDDLKKGTQLLEIYALEIQMYTAQKNNKKLKALYEQSLHIKSAIPHPLIMGVIREC
GGKMHLREGEFEKAHTDFFEAFKNYDESGSPRRTTCLKYLVLANMLMKSGINPFDSQEAK
PYKNDPEILAMTNLVSAYQNNDITEFEKILKTNHSNIMDDPFIREHIEELLRNIRTQVLI
KLIKPYTRIHIPFISKELNIDVADVESLLVQCILDNTIHGRIDQVNQLLELDHQKRGGAR
YTALDKWTNQLNSLNQAVVSKLA
Sequence of entity 3 (C), FASTA
>9PH4_3 COP9 signalosome complex subunit 3 (chains C)
MASALEQFVNSVRQLSAQGQMTQLCELINKSGELLAKNLSHLDTVLGALDVQEHSLGVLA
VLFVKFSMPSVPDFETLFSQVQLFISTCNGEHIRYATDTFAGLCHQLTNALVERKQPLRG
IGILKQAIDKMQMNTNQLTSIHADLCQLCLLAKCFKPALPYLDVDMMDICKENGAYDAKH
FLCYYYYGGMIYTGLKNFERALYFYEQAITTPAMAVSHIMLESYKKYILVSLILLGKVQQ
LPKYTSQIVGRFIKPLSNAYHELAQVYSTNNPSELRNLVNKHSETFTRDNNMGLVKQCLS
SLYKKNIQRLTKTFLTLSLQDMASRVQLSGPQEAEKYVLHMIEDGEIFASINQKDGMVSF
HDNPEKYNNPAMLHNIDQEMLKCIELDERLKAMDQEITVNPQFVQKSMGSQEDDSGNKPS
SYS
Sequence of entity 4 (D), FASTA
>9PH4_4 COP9 signalosome complex subunit 4 (chains D)
MAAAVRQDLAQLMNSSGSHKDLAGKYRQILEKAIQLSGAEQLEALKAFVEAMVNENVSLV
ISRQLLTDFCTHLPNLPDSTAKEIYHFTLEKIQPRVISFEEQVASIRQHLASIYEKEEDW
RNAAQVLVGIPLETGQKQYNVDYKLETYLKIARLYLEDDDPVQAEAYINRASLLQNESTN
EQLQIHYKVCYARVLDYRRKFIEAAQRYNELSYKTIVHESERLEALKHALHCTILASAGQ
QRSRMLATLFKDERCQQLAAYGILEKMYLDRIIRGNQLQEFAAMLMPHQKATTADGSSIL
DRAVIEHNLLSASKLYNNITFEELGALLEIPAAKAEKIASQMITEGRMNGFIDQIDGIVH
FETREALPTWDKQIQSLCFQVNNLLEKISQTAPEWTAQAMEAQMAQ
Sequence of entity 5 (E), FASTA
>9PH4_5 COP9 signalosome complex subunit 5 (chains E)
MAASGSGMAQKTWELANNMQEAQSIDEIYKYDKKQQQEILAAKPWTKDHHYFKYCKISAL
ALLKMVMHARSGGNLEVMGLMLGKVDGETMIIMDSFALPVEGTETRVNAQAAAYEYMAAY
IENAKQVGRLENAIGWYHSHPGYGCWLSGIDVSTQMLNQQFQEPFVAVVIDPTRTISAGK
VNLGAFRTYPKGYKPPDEGPSEYQTIPLNKIEDFGVHCKQYYALEVSYFKSSLDRKLLEL
LWNKYWVNTLSSSSLLTNADYTTGQVFDLSEKLEQSEAQLGRGSFMLGLETHDRKSEDKL
AKATRDSCKTTIEAIHGLMSQVIKDKLFNQINIS
Sequence of entity 6 (F), FASTA
>9PH4_6 COP9 signalosome complex subunit 6 (chains F)
MAAAAAAAAATNGTGGSSGMEVDAAVVPSVMACGVTGSVSVALHPLVILNISDHWIRMRS
QEGRPVQVIGALIGKQEGRNIEVMNSFELLSHTVEEKIIIDKEYYYTKEEQFKQVFKELE
FLGWYTTGGPPDPSDIHVHKQVCEIIESPLFLKLNPMTKHTDLPVSVFESVIDIINGEAT
MLFAELTYTLATEEAERIGVDHVARMTATGSGENSTVAEHLIAQHSAIKMLHSRVKLILE
YVKASEAGEVPFNHEILREAYALCHCLPVLSTDKFKTDFYDQCNDVGLMAYLGTITKTCN
TMNQFVNKFNVLYDRQGIGRRMRGLFF
Sequence of entity 7 (G), FASTA
>9PH4_7 COP9 signalosome complex subunit 7b (chains G)
MAGEQKPSSNLLEQFILLAKGTSGSALTALISQVLEAPGVYVFGELLELANVQELAEGAN
AAYLQLLNLFAYGTYPDYIANKESLPELSTAQQNKLKHLTIVSLASRMKCIPYSVLLKDL
EMRNLRELEDLIIEAVYTDIIQGKLDQRNQLLEVDFCIGRDIRKKDINNIVKTLHEWCDG
CEAVLLGIEQQVLRANQYKENHNRTQQQVEAEVTNIKKTLKATASSSAQEMEQQLAEREC
PPHAEQRQPTKKMSKVKGLVSSRH
Sequence of entity 8 (H), FASTA
>9PH4_8 COP9 signalosome complex subunit 8 (chains H)
MPVAVMAESAFSFKKLLDQCENQELEAPGGIATPPVYGQLLALYLLHNDMNNARYLWKRI
PPAIKSANSELGGIWSVGQRIWQRDFPGIYTTINAHQWSETVQPIMEALRDATRRRAFAL
VSQAYTSIIADDFAAFVGLPVEEAVKGILEQGWQADSTTRMVLPRKPVAGALDVSFNKFI
PLSEPAPVPPIPNEQQLARLTDYVAFLEN
Ligands and cofactors
| ID | Name | Formula | Copies |
|---|
| ZN | Zinc ion | Zn | 1 |
| A1CH3 | 6-[(4R,5S,6S)-6-hydroxy-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl][1,1'-b… | C21 H19 N3 O | 1 |
Primary citation
CSN5i-3 is an orthosteric molecular glue inhibitor of COP9 signalosome. Shi, H., Wang, X., Yu, C. et al. Nature (2026) 652:1375-1383. DOI 10.1038/s41586-026-10129-y · PubMed
Other PDB entries of the same protein (UniProt Q13098 (AlphaFold model), which also has an AlphaFold model), best resolution first:
- 9QO4 2.95 Å, Dissociation-state-3 of 9-subunit CSN and SCF (SKP1-SKP2-CKS1) complex
- 9EFQ 2.96 Å, Cryo-EM structure of COP9 signalosome precatalytic state with neddylated cullin-2
- 9QO6 3.0 Å, 9-subunit COP9 signalosome complex
- 9EFV 3.03 Å, Cryo-EM structure of CSN-N8CUL1 in complex with CSN5i-3
- 9EFM 3.16 Å, Cryo-EM structure of COP9 signalosome precatalytic state with neddylated cullin-1
- 9QO1 3.23 Å, Activated 9-subunit COP9 signalosome and neddylated SCF (SKP1-SKP2-CKS1) complex structure
- 9QO0 3.26 Å, Pre-activated 9-subunit COP9 signalosome and neddylated SCF (Skp1-Skp2-Cks1) complex…
- 9E77 3.3 Å, Cryo-EM structure of CSN-N8 in complex with CSN5i-3
- 9E81 3.3 Å, Cryo-EM structure of COP9 signalosome in complex with CSN5i-3
- 9EG8 3.39 Å, Cryo-EM structure of COP9 signalosome precatalytic state with neddylated cullin-4A
- 9E5Z 3.4 Å, Cryo-EM structure of COP9 signalosome
- 9EG1 3.52 Å, COP9 signalosome deneddylation complex with cullin-5
Browse structure collections
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