8W2E: SARS-CoV-2 M protein dimer

SARS-CoV-2 M protein dimer in complex with JNJ-9676 and Fab-B. Determined by electron microscopy at 3.06 Å resolution. Released 29 Jan 2025.

Method: Electron microscopy
Resolution: 3.06 Å
Organisms: SARS-CoV-2 pseudovirus, Homo sapiens
Chains: 6
Atoms: 9,373
Mol. weight: 157.69 kDa
Ligands: A1AE8
Released: 29 Jan 2025

Explore 8W2E in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8W2E contains 29 α-helices and 106 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.

Chain A: 4 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	22-33	12
α-helix	44-70	27
α-helix	76-79	4
α-helix	81-105	25
β-strand	119-123	5	1
β-strand	128-132	5	1
β-strand	139-143	5	1
β-strand	149-150	2	1
β-strand	155-157	3	1
β-strand	166-170	5	1
β-strand	176-187	12	1
β-strand	191-202	12	1

Chain B: 4 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	22-33	12
α-helix	44-70	27
α-helix	76-79	4
α-helix	83-105	23
β-strand	119-122	4	2
β-strand	129-132	4	2
β-strand	139-143	5	2
β-strand	149-150	2	2
β-strand	155-157	3	2
β-strand	166-170	5	2
β-strand	176-187	12	2
β-strand	191-202	12	2

Chain C: 6 helices, 21 β-strands

Element	Residues	Length	Sheet
β-strand	5	1	3
β-strand	10-13	4	4
β-strand	19-21	3	3
β-strand	24	1	3
α-helix	31-33	3
β-strand	38-42	5	4
β-strand	49-52	4	4
β-strand	58	1	4
α-helix	59	1
β-strand	66-71	6	3
β-strand	74-79	6	3
β-strand	89-93	5	4
β-strand	102	1	4
β-strand	107-110	4	4
β-strand	115	1	5
β-strand	120-122	3	6
α-helix	123-125	3
α-helix	126-131	6
β-strand	133-143	11	6
β-strand	144	1	5
β-strand	149-152	4	7
β-strand	163-167	5	6
α-helix	168-171	4
β-strand	177-186	10	6
α-helix	187-190	4
β-strand	195-201	7	7
β-strand	209-214	6	7

Chain D: 4 helices, 21 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	8
β-strand	10-12	3	9
β-strand	18-19	2	10
β-strand	22-25	4	8
β-strand	35-40	6	11
β-strand	44-45	2	11
β-strand	49-51	3	11
β-strand	58-60	3	11
α-helix	62-64	3
β-strand	68-69	2	10
β-strand	72-73	2	12
β-strand	78-79	2	12
β-strand	82-83	2	10
α-helix	88-90	3
β-strand	92-97	6	11
β-strand	108	1	11
β-strand	109-111	3	9
α-helix	117-119	3
β-strand	120-123	4	13
β-strand	138-145	8	13
β-strand	151-154	4	14
β-strand	175-181	7	13
β-strand	194-199	6	14
α-helix	200-202	3
β-strand	204-209	6	14

Chain E: 10 helices, 22 β-strands

Element	Residues	Length	Sheet
β-strand	5	1	15
β-strand	10-13	4	16
β-strand	19-21	3	15
β-strand	24	1	15
α-helix	31-33	3
β-strand	38-42	5	16
β-strand	49-52	4	16
β-strand	58	1	16
α-helix	59	1
β-strand	66-71	6	15
β-strand	74-79	6	15
β-strand	89-93	5	16
α-helix	101	1
β-strand	102	1	16
α-helix	103	1
β-strand	106-110	5	16
β-strand	115	1	17
α-helix	116-117	2
β-strand	118-122	5	18
α-helix	123-125	3
α-helix	126-129	4
β-strand	133-143	11	18
β-strand	144	1	17
β-strand	148-154	7	19
β-strand	157-159	3	19
β-strand	163-167	5	18
α-helix	169-171	3
β-strand	177-186	10	18
α-helix	187-191	5
β-strand	195-202	8	19
α-helix	208	1
β-strand	209-214	6	19

Chain F: 1 helix, 26 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	20
β-strand	10-12	3	21
β-strand	18-19	2	22
β-strand	22-25	4	20
β-strand	30	1	23
β-strand	32	1	23
β-strand	35-40	6	24
β-strand	44-51	8	24
β-strand	58-60	3	24
β-strand	68-69	2	22
β-strand	72-73	2	25
β-strand	78-79	2	25
β-strand	82-83	2	22
α-helix	88-90	3
β-strand	92-97	6	24
β-strand	103	1	24
β-strand	108	1	24
β-strand	109-111	3	21
β-strand	117	1	26
β-strand	120-123	4	27
β-strand	136-145	10	27
β-strand	146	1	26
β-strand	151-154	4	28
β-strand	164-170	7	27
β-strand	175-183	9	27
β-strand	194-198	5	28
β-strand	206-209	4	28

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Membrane protein	A, B	protein	270	SARS-CoV-2 pseudovirus	P0DTC5 (AlphaFold model)
Fab B Heavy Chain	C, E	protein	220	Homo sapiens
Fab B Light Chain	D, F	protein	225	Homo sapiens

Sequence of entity 1 (A, B), FASTA

>8W2E_1 Membrane protein (chains A, B)
MADSNGTITVEELKKLLEQWNLVIGFLFLTWICLLQFAYANRNRFLYIIKLIFLWLLWPV
TLACFVLAAVYRINWITGGIAIAMACLVGLMWLSYFIASFRLFARTRSMWSFNPETNILL
NVPLHGTILTRPLLESELVIGAVILRGHLRIAGHHLGRCDIKDLPKEITVATSRTLSYYK
LGASQRVAGDSGFAAYSRYRIGNYKLNTDHSSSSDNIALLVQSNSLEVLFQGPSRGGSGA
AAGSGSGSGSPSRLEEELRRRLTEGSEPEA

Sequence of entity 2 (C, E), FASTA

>8W2E_2 Fab B Heavy Chain (chains C, E)
ASDIVMTQSPASLAVSLGQRATISCKASQSIDYDGDNYMNWYQQKPGQPPKLLIYTTSNL
ESGIPARFSGSGSGTDFTLNIHPVEEGDAATYYCQQNNEDPYTFGGGTKLEIKRADAAPT
VSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYS
MSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

Sequence of entity 3 (D, F), FASTA

>8W2E_3 Fab B Light Chain (chains D, F)
EVQLQQSGPELVKPGASMKISCKTSGYSFTGYTMNWVKQSHGKNLEWIGLINPYNGDTSY
NQKFKGKATLTVDKSSSTAYMELLSLTSEDSAVYYCEVINTYWGQGTLVTVSAAKTTPPS
VYPLAPGSAAQTNSMVTLGCLVKGYFPEPVTVTWNSGSLSSGVHTFPAVLQSDLYTLSSS
VTVPSSTWPSETVTCNVAHPASSTKVDKKIVPRDCGSGSHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
A1AE8	(6S,8R)-N-(3-cyanophenyl)-5-{4-[difluoro(phenyl)methyl]phenyl}-6-methyl-4-oxo-4…	C28 H21 F2 N5 O2	2

Primary citation

A small-molecule SARS-CoV-2 inhibitor targeting the membrane protein. Van Damme, E., Abeywickrema, P., Yin, Y. et al. Nature (2025) 640:506-513. DOI 10.1038/s41586-025-08651-6 · PubMed

Other PDB entries of the same protein (UniProt P0DTC5 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8CME 2.26 Å, Human Leukocyte Antigen class II allotype DR1 presenting SARS-CoV-2 Membrane peptide…
7VGR 2.7 Å, SARS-CoV-2 M protein dimer (long form) in complex with YN7756_1 Fab
7VGS 2.8 Å, SARS-CoV-2 M protein dimer (short form) in complex with YN7717_9 Fab
9CTW 3.01 Å, Cryo-EM structure of SARS-CoV-2 M (long conformation) in the presence of C1P
9CTU 3.03 Å, Cryo-EM structure of SARS-CoV-2 M (short conformation)bound to C1P
9EXA 3.2 Å, SARS-CoV-2 M protein dimer (short form) in complex with Fab-B and CIM-834
9BF9 3.4 Å, Human LAG-3-HLA-DR1 complex
8CTK 3.52 Å, Cryo-EM structure of SARS-CoV-2 M protein in a lipid nanodisc

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