8WSA: Mouse TLR4/MD-2/DLAM5 Complex

Cryo-EM Structure of Mouse TLR4/MD-2/DLAM5 Complex. Determined by electron microscopy at 3.1 Å resolution. Released 23 Oct 2024.

Method: Electron microscopy
Resolution: 3.1 Å
Organism: Mus musculus
Chains: 4
Atoms: 12,132
Mol. weight: 176.85 kDa
Ligands: GP4, A1L01, NAG, 2IL
Released: 23 Oct 2024

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

Secondary structure: helices and β-sheets

8WSA contains 16 α-helices and 88 β-strands across 4 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: 8 helices, 34 β-strands

Element	Residues	Length	Sheet
β-strand	32	1	1
β-strand	35	1	1
α-helix	52	1
β-strand	107	1	2
β-strand	131	1	2
β-strand	155	1	2
β-strand	157	1	3
α-helix	168-171	4
β-strand	182	1	3
α-helix	195-199	5
β-strand	226	1	4
β-strand	232-233	2	5
α-helix	239-248	10
β-strand	253	1	4
β-strand	259-260	2	5
β-strand	283	1	4
β-strand	289	1	5
α-helix	303-305	3
β-strand	313-314	2	5
β-strand	335-336	2	5
β-strand	356-357	2	5
β-strand	362-364	3	6
β-strand	378-379	2	5
β-strand	382-384	3	6
α-helix	391-393	3
β-strand	401	1	7
β-strand	410-411	2	8
β-strand	424	1	7
β-strand	427	1	9
β-strand	432-433	2	8
β-strand	452	1	9
β-strand	459	1	10
β-strand	481	1	10
β-strand	486	1	11
β-strand	498-500	3	12
β-strand	509	1	11
β-strand	522-526	5	12
β-strand	548-550	3	12
β-strand	579	1	13
α-helix	585-590	6
α-helix	601-603	3
β-strand	607	1	13

Chains C and D: 0 helices, 10 β-strands

Element	Residues	Length	Sheet
β-strand	24-26	3	27
β-strand	31-36	6	27
β-strand	45-49	5	28
β-strand	57-65	9	28
β-strand	75-82	8	27
β-strand	85-90	6	27
β-strand	93	1	27
β-strand	113-121	9	28
β-strand	130-138	9	27
β-strand	145-154	10	27

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Toll-like receptor 4	A, B	protein	604	Mus musculus	Q9QUK6 (AlphaFold model)
Lymphocyte antigen 96	C, D	protein	142	Mus musculus	Q9JHF9 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>8WSA_1 Toll-like receptor 4 (chains A, B)
NPCIEVVPNITYQCMDQKLSKVPDDIPSSTKNIDLSFNPLKILKSYSFSNFSELQWLDLS
RCEIETIEDKAWHGLHHLSNLILTGNPIQSFSPGSFSGLTSLENLVAVETKLASLESFPI
GQLITLKKLNVAHNFIHSCKLPAYFSNLTNLVHVDLSYNYIQTITVNDLQFLRENPQVNL
SLDMSLNPIDFIQDQAFQGIKLHELTLRGNFNSSNIMKTCLQNLAGLHVHRLILGEFKDE
RNLEIFEPSIMEGLCDVTIDEFRLTYTNDFSDDIVKFHCLANVSAMSLAGVSIKYLEDVP
KHFKWQSLSIIRCQLKQFPTLDLPFLKSLTLTMNKGSISFKKVALPSLSYLDLSRNALSF
SGCCSYSDLGTNSLRHLDLSFNGAIIMSANFMGLEELQHLDFQHSTLKRVTEFSAFLSLE
KLLYLDISYTNTKIDFDGIFLGLTSLNTLKMAGNSFKDNTLSNVFANTTNLTFLDLSKCQ
LEQISWGVFDTLHRLQLLNMSHNNLLFLDSSHYNQLYSLSTLDCSFNRIETSKGILQHFP
KSLAFFNLTNNSVACICEHQKFLQWVKEQKQFLVNVEQMTCATPVEMNTSLVLDFNNSTC
YMYK

Sequence of entity 2 (C, D), FASTA

>8WSA_2 Lymphocyte antigen 96 (chains C, D)
EKQQWFCNSSDAIISYSYCDHLKFPISISSEPCIRLRGTNGFVHVEFIPRGNLKYLYFNL
FISVNSIELPKRKEVLCHGHDDDYSFCRALKGETVNTSIPFSFEGILFPKGHYRCVAEAI
AGDTEEKLFCLNFTIIHRRDVN

Ligands and cofactors

ID	Name	Formula	Copies
GP4	2-amino-2-deoxy-4-O-phosphono-alpha-D-glucopyranose	C6 H14 N O8 P	2
A1L01	(3~{S})-3-decanoyloxytetradecanoic acid	C24 H46 O4	2
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	14
2IL	(3R)-3-(dodecanoyloxy)tetradecanoic acid	C26 H50 O4	2
0IL	(3R)-3-(tetradecanoyloxy)tetradecanoic acid	C28 H54 O4	2
X6N	[(2~{R},3~{S},4~{R},5~{S})-2-(hydroxymethyl)-5-methoxy-4,6-bis(oxidanyl)oxan-3-…	C7 H15 O9 P	2

Primary citation

Structural insight into TLR4/MD-2 activation by synthetic LPS mimetics with distinct binding modes. Fu, Y., Kim, H., Lee, D.S. et al. Nat Commun (2025) 16:4164-4164. DOI 10.1038/s41467-025-59550-3 · PubMed

Other PDB entries of the same protein (UniProt Q9QUK6 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7MLM 2.1 Å, Crystal structure of mouse TLR4/MD-2 in complex with sulfatides
3VQ2 2.48 Å, Crystal structure of mouse TLR4/MD-2/LPS complex
5IJC 2.57 Å, The crystal structure of mouse TLR4/MD-2/neoseptin-3 complex
8WQT 2.6 Å, Cryo-EM Structure of Mouse TLR4/MD-2/DLAM1 complex
8WRY 2.6 Å, Cryo-EM Structure of Mouse TLR4/MD-2/DLAM3 Complex
3VQ1 2.7 Å, Crystal structure of mouse TLR4/MD-2/lipid IVa complex
5IJD 2.7 Å, The crystal structure of mouse TLR4/MD-2/lipid A complex
2Z64 2.84 Å, Crystal structure of mouse TLR4 and mouse MD-2 complex
5IJB 2.91 Å, The ligand-free structure of the mouse TLR4/MD-2 complex

Browse structure collections

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