9M2W: 26S proteasome-Midnolin complex in the MD state

The cryo-EM structure of 26S proteasome-Midnolin complex in the MD state. Determined by electron microscopy at 3.31 Å resolution. Released 10 Sept 2025.

Method: Electron microscopy
Resolution: 3.31 Å
Organism: Homo sapiens
Chains: 48
Atoms: 98,427
Mol. weight: 1718.88 kDa
Ligands: ATP, ADP
Released: 10 Sept 2025

Explore 9M2W in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9M2W contains 591 α-helices and 511 β-strands across 47 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: 24 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	7-11	5
α-helix	18-31	14
α-helix	34-46	13
α-helix	53-66	14
α-helix	72-87	16
α-helix	93-103	11
α-helix	109-125	17
α-helix	130-136	7
α-helix	138-142	5
α-helix	150-165	16
α-helix	169-182	14
α-helix	190-200	11
α-helix	201-205	5
α-helix	206	1
α-helix	220-226	7
α-helix	231-240	10
α-helix	247-256	10
α-helix	265-283	19
α-helix	287-289	3
α-helix	293-299	7
α-helix	304-316	13
β-strand	325	1	7
β-strand	330	1	7
α-helix	340-341	2
α-helix	346-348	3
α-helix	355-375	21

Chain A: 22 helices, 18 β-strands

Element	Residues	Length	Sheet
α-helix	27-31	5
α-helix	32-34	3
α-helix	42-63	22
β-strand	72	1	1
α-helix	73-74	2
α-helix	85-90	6
β-strand	96-100	5	2
β-strand	111	1	3
β-strand	114	1	2
β-strand	120	1	2
β-strand	123	1	3
α-helix	124	1
β-strand	125	1	2
α-helix	126	1
β-strand	139-143	5	2
β-strand	149-152	4	2
α-helix	154-156	3
α-helix	159-164	6
β-strand	165	1	4
α-helix	181-191	11
α-helix	193-196	4
α-helix	198-204	7
β-strand	211-215	5	4
α-helix	222-232	11
β-strand	236-238	3	4
α-helix	242-245	4
α-helix	252-266	15
β-strand	270-275	6	4
α-helix	293-306	14
β-strand	315-321	7	4
α-helix	324-326	3
α-helix	329-332	4
β-strand	339-342	4	4
α-helix	348-359	12
β-strand	364	1	5
α-helix	370-376	7
α-helix	382-398	17
β-strand	404	1	5
α-helix	406-416	11
β-strand	432	1	6

Chain b: 8 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	4-10	7	9
β-strand	13	1	10
α-helix	14-17	4
α-helix	25-43	19
β-strand	48-53	6	9
β-strand	55	1	11
β-strand	60	1	9
β-strand	65	1	9
α-helix	68-75	8
β-strand	81	1	10
β-strand	84	1	11
α-helix	86-99	14
β-strand	106-113	8	9
α-helix	121-133	13
β-strand	138	1	9
β-strand	141-142	2	9
α-helix	152-160	9
β-strand	171	1	9
α-helix	173-174	2
α-helix	180-189	10

Chain B: 15 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	59-80	22
α-helix	96-102	7
β-strand	107-112	6	2
β-strand	122-124	3	2
β-strand	131-132	2	2
β-strand	139	1	1
β-strand	149-153	5	2
β-strand	159	1	2
α-helix	169-172	4
β-strand	176	1	8
α-helix	191-197	7
α-helix	198-202	5
α-helix	209-214	6
α-helix	216-219	4
β-strand	221-225	5	8
α-helix	232-241	10
β-strand	246-251	6	8
α-helix	264-276	13
β-strand	280-285	6	8
α-helix	305-316	12
β-strand	326-331	6	8
β-strand	349-352	4	8
α-helix	354-356	3
α-helix	359-370	12
α-helix	380-386	7
α-helix	392-408	17
α-helix	416-426	11

Chain c: 14 helices, 9 β-strands

Element	Residues	Length	Sheet
β-strand	30-33	4	14
α-helix	35-47	13
α-helix	49-51	3
β-strand	54-61	8	14
β-strand	66-73	8	14
α-helix	75-77	3
α-helix	84-86	3
α-helix	89-101	13
β-strand	111-114	4	14
α-helix	124-136	13
β-strand	142-145	4	14
β-strand	158-160	3	14
β-strand	162	1	15
α-helix	178-185	8
α-helix	191-196	6
β-strand	200	1	15
β-strand	204-207	4	14
α-helix	212-220	9
α-helix	221-225	5
α-helix	249-263	15
α-helix	265-272	8
α-helix	289-303	15
α-helix	304-308	5

Chain C: 20 helices, 13 β-strands

Element	Residues	Length	Sheet
α-helix	24-27	4
α-helix	29-36	8
α-helix	38-62	25
α-helix	63-67	5
α-helix	69-70	2
β-strand	71-80	10	2
β-strand	84-89	6	2
β-strand	94-98	5	2
α-helix	105-107	3
β-strand	113-116	4	2
β-strand	122-127	6	2
α-helix	134-138	5
α-helix	155-170	16
α-helix	172-178	7
α-helix	181-183	3
β-strand	185-189	5	12
α-helix	196-205	10
β-strand	210-211	2	12
β-strand	214	1	12
α-helix	233-240	8
β-strand	244-248	5	12
α-helix	270-280	11
β-strand	289-295	7	12
α-helix	298-300	3
α-helix	303-306	4
β-strand	313-316	4	12
α-helix	318-320	3
α-helix	322-332	11
β-strand	338	1	13
α-helix	344-349	6
α-helix	357-372	16
β-strand	378	1	13
α-helix	380-390	11

Chain d: 14 helices, 0 β-strands

Element	Residues	Length
α-helix	111-125	15
α-helix	135-157	23
α-helix	161-176	16
α-helix	186-201	16
α-helix	205-214	10
α-helix	216-219	4
α-helix	224-237	14
α-helix	240-250	11
α-helix	259-265	7
α-helix	270-272	3
α-helix	301-304	4
α-helix	305-307	3
α-helix	316-318	3
α-helix	330-347	18

Chain D: 15 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	40-82	43
β-strand	87-97	11	2
β-strand	100-105	6	2
β-strand	110-113	4	2
β-strand	115	1	2
α-helix	121-124	4
β-strand	130-133	4	2
β-strand	139-142	4	2
α-helix	143-145	3
α-helix	171-177	7
α-helix	178-182	5
α-helix	183-185	3
α-helix	189-194	6
β-strand	201-205	5	16
α-helix	213-221	9
α-helix	243-256	14
β-strand	261-264	4	16
α-helix	268-271	4
α-helix	284-297	14
β-strand	306-309	4	16
β-strand	324	1	17
β-strand	326	1	17
β-strand	329-332	4	16
α-helix	341-349	9
α-helix	360-365	6
α-helix	372-388	17
α-helix	396-406	11

39 more chain groups are not listed. Open the entry in the viewer and use the sequence panel to see them.

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
26S proteasome regulatory subunit 7	A	protein	433	Homo sapiens	P35998 (AlphaFold model)
26S proteasome regulatory subunit 4	B	protein	440	Homo sapiens	P62191 (AlphaFold model)
26S proteasome regulatory subunit 8	C	protein	406	Homo sapiens	P62195 (AlphaFold model)
26S proteasome regulatory subunit 6B	D	protein	418	Homo sapiens	P43686 (AlphaFold model)
26S proteasome regulatory subunit 10B	E	protein	389	Homo sapiens	P62333
26S proteasome regulatory subunit 6A	F	protein	439	Homo sapiens	P17980
Proteasome subunit alpha type-6	G, g	protein	246	Homo sapiens	P60900
Proteasome subunit alpha type-2	H, h	protein	234	Homo sapiens	P25787
Proteasome subunit alpha type-4	I, i	protein	261	Homo sapiens	P25789
Proteasome subunit alpha type-7	J, j	protein	248	Homo sapiens	O14818
Proteasome subunit alpha type-5	K, k	protein	241	Homo sapiens	P28066
Proteasome subunit alpha type-1	L, l	protein	263	Homo sapiens	P25786

22 more molecules are not listed.

Sequence of entity 1 (A), FASTA

>9M2W_1 26S proteasome regulatory subunit 7 (chains A)
MPDYLGADQRKTKEDEKDDKPIRALDEGDIALLKTYGQSTYSRQIKQVEDDIQQLLKKIN
ELTGIKESDTGLAPPALWDLAADKQTLQSEQPLQVARCTKIINADSEDPKYIINVKQFAK
FVVDLSDQVAPTDIEEGMRVGVDRNKYQIHIPLPPKIDPTVTMMQVEEKPDVTYSDVGGC
KEQIEKLREVVETPLLHPERFVNLGIEPPKGVLLFGPPGTGKTLCARAVANRTDACFIRV
IGSELVQKYVGEGARMVRELFEMARTKKACLIFFDEIDAIGGARFDDGAGGDNEVQRTML
ELINQLDGFDPRGNIKVLMATNRPDTLDPALMRPGRLDRKIEFSLPDLEGRTHIFKIHAR
SMSVERDIRFELLARLCPNSTGAEIRSVCTEAGMFAIRARRKIATEKDFLEAVNKVIKSY
AKFSATPRYMTYN

Sequence of entity 2 (B), FASTA

>9M2W_2 26S proteasome regulatory subunit 4 (chains B)
MGQSQSGGHGPGGGKKDDKDKKKKYEPPVPTRVGKKKKKTKGPDAASKLPLVTPHTQCRL
KLLKLERIKDYLLMEEEFIRNQEQMKPLEEKQEEERSKVDDLRGTPMSVGTLEEIIDDNH
AIVSTSVGSEHYVSILSFVDKDLLEPGCSVLLNHKVHAVIGVLMDDTDPLVTVMKVEKAP
QETYADIGGLDNQIQEIKESVELPLTHPEYYEEMGIKPPKGVILYGPPGTGKTLLAKAVA
NQTSATFLRVVGSELIQKYLGDGPKLVRELFRVAEEHAPSIVFIDEIDAIGTKRYDSNSG
GEREIQRTMLELLNQLDGFDSRGDVKVIMATNRIETLDPALIRPGRIDRKIEFPLPDEKT
KKRIFQIHTSRMTLADDVTLDDLIMAKDDLSGADIKAICTEAGLMALRERRMKVTNEDFK
KSKENVLYKKQEGTPEGLYL

Sequence of entity 3 (C), FASTA

>9M2W_3 26S proteasome regulatory subunit 8 (chains C)
MALDGPEQMELEEGKAGSGLRQYYLSKIEELQLIVNDKSQNLRRLQAQRNELNAKVRLLR
EELQLLQEQGSYVGEVVRAMDKKKVLVKVHPEGKFVVDVDKNIDINDVTPNCRVALRNDS
YTLHKILPNKVDPLVSLMMVEKVPDSTYEMIGGLDKQIKEIKEVIELPVKHPELFEALGI
AQPKGVLLYGPPGTGKTLLARAVAHHTDCTFIRVSGSELVQKFIGEGARMVRELFVMARE
HAPSIIFMDEIDSIGSSRLEGGSGGDSEVQRTMLELLNQLDGFEATKNIKVIMATNRIDI
LDSALLRPGRIDRKIEFPPPNEEARLDILKIHSRKMNLTRGINLRKIAELMPGASGAEVK
GVCTEAGMYALRERRVHVTQEDFEMAVAKVMQKDSEKNMSIKKLWK

Sequence of entity 4 (D), FASTA

>9M2W_4 26S proteasome regulatory subunit 6B (chains D)
MEEIGILVEKAQDEIPALSVSRPQTGLSFLGPEPEDLEDLYSRYKKLQQELEFLEVQEEY
IKDEQKNLKKEFLHAQEEVKRIQSIPLVIGQFLEAVDQNTAIVGSTTGSNYYVRILSTID
RELLKPNASVALHKHSNALVDVLPPEADSSIMMLTSDQKPDVMYADIGGMDIQKQEVREA
VELPLTHFELYKQIGIDPPRGVLMYGPPGCGKTMLAKAVAHHTTAAFIRVVGSEFVQKYL
GEGPRMVRDVFRLAKENAPAIIFIDEIDAIATKRFDAQTGADREVQRILLELLNQMDGFD
QNVNVKVIMATNRADTLDPALLRPGRLDRKIEFPLPDRRQKRLIFSTITSKMNLSEEVDL
EDYVARPDKISGADINSICQESGMLAVRENRYIVLAKDFEKAYKTVIKKDEQEHEFYK

Sequence of entity 5 (E), FASTA

>9M2W_5 26S proteasome regulatory subunit 10B (chains E)
MADPRDKALQDYRKKLLEHKEIDGRLKELREQLKELTKQYEKSENDLKALQSVGQIVGEV
LKQLTEEKFIVKATNGPRYVVGCRRQLDKSKLKPGTRVALDMTTLTIMRYLPREVDPLVY
NMSHEDPGNVSYSEIGGLSEQIRELREVIELPLTNPELFQRVGIIPPKGCLLYGPPGTGK
TLLARAVASQLDCNFLKVVSSSIVDKYIGESARLIREMFNYARDHQPCIIFMDEIDAIGG
RRFSEGTSADREIQRTLMELLNQMDGFDTLHRVKMIMATNRPDTLDPALLRPGRLDRKIH
IDLPNEQARLDILKIHAGPITKHGEIDYEAIVKLSDGFNGADLRNVCTEAGMFAIRADHD
FVVQEDFMKAVRKVADSKKLESKLDYKPV

Sequence of entity 6 (F), FASTA

>9M2W_6 26S proteasome regulatory subunit 6A (chains F)
MNLLPNIESPVTRQEKMATVWDEAEQDGIGEEVLKMSTEEIIQRTRLLDSEIKIMKSEVL
RVTHELQAMKDKIKENSEKIKVNKTLPYLVSNVIELLDVDPNDQEEDGANIDLDSQRKGK
CAVIKTSTRQTYFLPVIGLVDAEKLKPGDLVGVNKDSYLILETLPTEYDSRVKAMEVDER
PTEQYSDIGGLDKQIQELVEAIVLPMNHKEKFENLGIQPPKGVLMYGPPGTGKTLLARAC
AAQTKATFLKLAGPQLVQMFIGDGAKLVRDAFALAKEKAPSIIFIDELDAIGTKRFDSEK
AGDREVQRTMLELLNQLDGFQPNTQVKVIAATNRVDILDPALLRSGRLDRKIEFPMPNEE
ARARIMQIHSRKMNVSPDVNYEELARCTDDFNGAQCKAVCVEAGMIALRRGATELTHEDY
MEGILEVQAKKKANLQYYA

Sequence of entity 7 (G, g), FASTA

>9M2W_7 Proteasome subunit alpha type-6 (chains G, g)
MSRGSSAGFDRHITIFSPEGRLYQVEYAFKAINQGGLTSVAVRGKDCAVIVTQKKVPDKL
LDSSTVTHLFKITENIGCVMTGMTADSRSQVQRARYEAANWKYKYGYEIPVDMLCKRIAD
ISQVYTQNAEMRPLGCCMILIGIDEEQGPQVYKCDPAGYYCGFKATAAGVKQTESTSFLE
KKVKKKFDWTFEQTVETAITCLSTVLSIDFKPSEIEVGVVTVENPKFRILTEAEIDAHLV
ALAERD

Sequence of entity 8 (H, h), FASTA

>9M2W_8 Proteasome subunit alpha type-2 (chains H, h)
MAERGYSFSLTTFSPSGKLVQIEYALAAVAGGAPSVGIKAANGVVLATEKKQKSILYDER
SVHKVEPITKHIGLVYSGMGPDYRVLVHRARKLAQQYYLVYQEPIPTAQLVQRVASVMQE
YTQSGGVRPFGVSLLICGWNEGRPYLFQSDPSGAYFAWKATAMGKNYVNGKTFLEKRYNE
DLELEDAIHTAILTLKESFEGQMTEDNIEVGICNEAGFRRLTPTEVKDYLAAIA

Sequence of entity 9 (I, i), FASTA

>9M2W_9 Proteasome subunit alpha type-4 (chains I, i)
MSRRYDSRTTIFSPEGRLYQVEYAMEAIGHAGTCLGILANDGVLLAAERRNIHKLLDEVF
FSEKIYKLNEDMACSVAGITSDANVLTNELRLIAQRYLLQYQEPIPCEQLVTALCDIKQA
YTQFGGKRPFGVSLLYIGWDKHYGFQLYQSDPSGNYGGWKATCIGNNSAAAVSMLKQDYK
EGEMTLKSALALAIKVLNKTMDVSKLSAEKVEIATLTRENGKTVIRVLKQKEVEQLIKKH
EEEEAKAEREKKEKEQKEKDK

Sequence of entity 10 (J, j), FASTA

>9M2W_10 Proteasome subunit alpha type-7 (chains J, j)
MSYDRAITVFSPDGHLFQVEYAQEAVKKGSTAVGVRGRDIVVLGVEKKSVAKLQDERTVR
KICALDDNVCMAFAGLTADARIVINRARVECQSHRLTVEDPVTVEYITRYIASLKQRYTQ
SNGRRPFGISALIVGFDFDGTPRLYQTDPSGTYHAWKANAIGRGAKSVREFLEKNYTDEA
IETDDLTIKLVIKALLEVVQSGGKNIELAVMRRDQSLKILNPEEIEKYVAEIEKEKEENE
KKKQKKAS

Sequence of entity 11 (K, k), FASTA

>9M2W_11 Proteasome subunit alpha type-5 (chains K, k)
MFLTRSEYDRGVNTFSPEGRLFQVEYAIEAIKLGSTAIGIQTSEGVCLAVEKRITSPLME
PSSIEKIVEIDAHIGCAMSGLIADAKTLIDKARVETQNHWFTYNETMTVESVTQAVSNLA
LQFGEEDADPGAMSRPFGVALLFGGVDEKGPQLFHMDPSGTFVQCDARAIGSASEGAQSS
LQEVYHKSMTLKEAIKSSLIILKQVMEEKLNATNIELATVQPGQNFHMFTKEELEEVIKD
I

Sequence of entity 12 (L, l), FASTA

>9M2W_12 Proteasome subunit alpha type-1 (chains L, l)
MFRNQYDNDVTVWSPQGRIHQIEYAMEAVKQGSATVGLKSKTHAVLVALKRAQSELAAHQ
KKILHVDNHIGISIAGLTADARLLCNFMRQECLDSRFVFDRPLPVSRLVSLIGSKTQIPT
QRYGRRPYGVGLLIAGYDDMGPHIFQTCPSANYFDCRAMSIGARSQSARTYLERHMSEFM
ECNLNELVKHGLRALRETLPAEQDLTTKNVSIGIVGKDLEFTIYDDDDVSPFLEGLEERP
QRKAQPAQPADEPAEKADEPMEH

Ligands and cofactors

ID	Name	Formula	Copies
ATP	Adenosine-5'-triphosphate	C10 H16 N5 O13 P3	4
ADP	Adenosine-5'-diphosphate	C10 H15 N5 O10 P2	1

Primary citation

Structure-based engineering of the midnolin-proteasome pathway for targeted protein degradation. Wang, H., Zheng, Y., Wang, T. et al. Protein Cell (2026) 17:83-88. DOI 10.1093/procel/pwaf069 · PubMed

Other PDB entries of the same protein (UniProt P35998 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9K53 2.5 Å, Structure of substrate-engaged human 26S proteasome RP-CP subcomplex in state ED2.1
8USD 2.7 Å, Rpn1/Nub1UBL-focused alignment of the non-substrate-engaged human 26S proteasome
8USB 2.73 Å, Non-substrate-engaged human 26S proteasome with Nub1/FAT10 bound to Rpn1
9MBP 2.75 Å, Substrate-engaged human 26S proteasome bound to midnolin with RPT1 at top of spiral…
9PDL 2.76 Å, Nub1/Fat10-processing human 26S proteasome with Rpt5 at top of spiral staircase (AAA+…
9NKG 2.8 Å, Structure of substrate engaged MIDN-bound human 26S proteasome, EB-MIDN (Composite map)
9E8I 2.87 Å, Human proteasome in resting state conformation bound to TXNL1 in Forward conformation
9BV3 2.9 Å, M1B Midnolin-Proteasome
9E8H 2.9 Å, Human proteasome in resting state conformation bound to TXNL1 in backward conformation
9K4J 2.9 Å, Structure of substrate-engaged human 26S proteasome RP-CP subcomplex in state EA1.0
9NKF 2.9 Å, Structure of human substrate-free 26S proteasome in the presence of ATPgS and…
9U3L 2.91 Å, Substrate-engaged human 26S proteasome bound to midnolin with RPT2 at top of spiral…

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