IntAct European Bioinformatics Institute IntAct intact http://www.ebi.ac.uk/ http://www.ebi.ac.uk/intact/query/${ac} EBI-[0-9]+|IA:[0-9]+ INTerAction database (IntAct) provides an open source database and toolkit for the storage, presentation and analysis of molecular interactions. http://www.ebi.ac.uk/intact European Bioinformatics Institute; Wellcome Trust Genome Campus; Hinxton, Cambridge; CB10 1SD; United Kingdom http://www.ebi.ac.uk/intact/ http://www.ebi.ac.uk/ kim-2007a-2 Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. in vitro In vitro molecular sieving molecular sieving Gel Filtration Size Exclusion Chromatography Size Exclusion Chromatography Gel Filtration Sizing column predetermined predetermined participant predetermined Kim HM., Park BS., Kim JI., Kim SE., Lee J., Oh SC., Enkhbayar P., Matsushima N., Lee H., Yoo OJ., Lee JO. Native PAGE analysis of TLR4-MD-2 complexes was carried out. The expression system for proteins is found in the pdb entry for the complex. The UniProtKB accession number for the hagfish VLR protein found in the hybrids was determined by taking the appropriate sequence from the pdb entry. (Table S2 was used to help determine this sequence). This sequence was used in MPsrch to find the UniProtKB accession number. The authors specify that the ectodomains of TLR4 and MD-2 form a complex but do not give the ranges of the ectodomains. The UniProtKB entry gives the extracellular domain of TLR4 as aa 26-638. The authors state MD-2 lacks transmembrane and intracellular domains. jieoh.lee@kaist.ac.kr Cell (0092-8674) 2007 Only protein-protein interactions 8 imex curation kim-2007a-3 Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. in vitro In vitro molecular sieving molecular sieving Gel Filtration Size Exclusion Chromatography Size Exclusion Chromatography Gel Filtration Sizing column predetermined predetermined participant predetermined Kim HM., Park BS., Kim JI., Kim SE., Lee J., Oh SC., Enkhbayar P., Matsushima N., Lee H., Yoo OJ., Lee JO. Native PAGE analysis of TLR4-MD-2 complexes was carried out. The expression system for proteins is found in the pdb entry for the complex. The UniProtKB accession number for the hagfish VLR protein found in the hybrids was determined by taking the appropriate sequence from the pdb entry. (Table S2 was used to help determine this sequence). This sequence was used in MPsrch to find the UniProtKB accession number. The authors specify that the ectodomains of TLR4 and MD-2 form a complex but do not give the ranges of the ectodomains. The UniProtKB entry gives the extracellular domain of TLR4 as aa 26-638. The authors state MD-2 lacks transmembrane and intracellular domains. jieoh.lee@kaist.ac.kr Cell (0092-8674) 2007 Only protein-protein interactions 8 imex curation kim-2007a-1 Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. in vitro In vitro x-ray diffraction x-ray crystallography X-ray X-ray x-ray diffraction predetermined predetermined participant predetermined Kim HM., Park BS., Kim JI., Kim SE., Lee J., Oh SC., Enkhbayar P., Matsushima N., Lee H., Yoo OJ., Lee JO. Native PAGE analysis of TLR4-MD-2 complexes was carried out. The expression system for proteins is found in the pdb entry for the complex. The UniProtKB accession number for the hagfish VLR protein found in the hybrids was determined by taking the appropriate sequence from the pdb entry. (Table S2 was used to help determine this sequence). This sequence was used in MPsrch to find the UniProtKB accession number. The authors specify that the ectodomains of TLR4 and MD-2 form a complex but do not give the ranges of the ectodomains. The UniProtKB entry gives the extracellular domain of TLR4 as aa 26-638. The authors state MD-2 lacks transmembrane and intracellular domains. jieoh.lee@kaist.ac.kr Cell (0092-8674) 2007 Only protein-protein interactions 8 imex curation kim-2007a-4 Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. in vitro In vitro crosslink cross-linking study crosslink western blot western blot Immuno blot Immuno blot Kim HM., Park BS., Kim JI., Kim SE., Lee J., Oh SC., Enkhbayar P., Matsushima N., Lee H., Yoo OJ., Lee JO. Native PAGE analysis of TLR4-MD-2 complexes was carried out. The expression system for proteins is found in the pdb entry for the complex. The UniProtKB accession number for the hagfish VLR protein found in the hybrids was determined by taking the appropriate sequence from the pdb entry. (Table S2 was used to help determine this sequence). This sequence was used in MPsrch to find the UniProtKB accession number. The authors specify that the ectodomains of TLR4 and MD-2 form a complex but do not give the ranges of the ectodomains. The UniProtKB entry gives the extracellular domain of TLR4 as aa 26-638. The authors state MD-2 lacks transmembrane and intracellular domains. jieoh.lee@kaist.ac.kr Cell (0092-8674) 2007 Only protein-protein interactions 8 imex curation ly96_human Lymphocyte antigen 96 Protein MD-2 ESOP-1 LY96 ESOP1 MD2 protein protein human Homo sapiens Human MLPFLFFSTLFSSIFTEAQKQYWVCNSSDASISYTYCDKMQYPISINVNPCIELKRSKGLLHIFYIPRRDLKQLYFNLYITVNTMNLPKRKEVICRGSDDDYSFCRALKGETVNTTISFSFKGIKFSKGKYKCVVEAISGSPEEMLFCLEFVILHQPNSN tlr4_q4g1l2_tv8_prot TV8 hybrid of human TLR4 and Hagfish VLR protein protein human Homo sapiens Human EPCVEVVPNITYQCMELNFYKIPDNLPFSTKNLDLSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALGAFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHLDLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSLNVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRLAYLDYYLDDIIDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTSNKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLGLEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFNGIFNGLSSLEVLKMAGNSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMNQLKSVPDGIFDRLTSLQKIWLHTNPWDCSCPRIDYLSRWLNKNSQKEQGSAKCSGSGKPVRSIICPT An amino acid sequence which is not represented in UniProt tlr4_mouse Toll-like receptor 4 Tlr4 Lps protein protein mouse Mus musculus Mouse MMPPWLLARTLIMALFFSCLTPGSLNPCIEVVPNITYQCMDQKLSKVPDDIPSSTKNIDLSFNPLKILKSYSFSNFSELQWLDLSRCEIETIEDKAWHGLHHLSNLILTGNPIQSFSPGSFSGLTSLENLVAVETKLASLESFPIGQLITLKKLNVAHNFIHSCKLPAYFSNLTNLVHVDLSYNYIQTITVNDLQFLRENPQVNLSLDMSLNPIDFIQDQAFQGIKLHELTLRGNFNSSNIMKTCLQNLAGLHVHRLILGEFKDERNLEIFEPSIMEGLCDVTIDEFRLTYTNDFSDDIVKFHCLANVSAMSLAGVSIKYLEDVPKHFKWQSLSIIRCQLKQFPTLDLPFLKSLTLTMNKGSISFKKVALPSLSYLDLSRNALSFSGCCSYSDLGTNSLRHLDLSFNGAIIMSANFMGLEELQHLDFQHSTLKRVTEFSAFLSLEKLLYLDISYTNTKIDFDGIFLGLTSLNTLKMAGNSFKDNTLSNVFANTTNLTFLDLSKCQLEQISWGVFDTLHRLQLLNMSHNNLLFLDSSHYNQLYSLSTLDCSFNRIETSKGILQHFPKSLAFFNLTNNSVACICEHQKFLQWVKEQKQFLVNVEQMTCATPVEMNTSLVLDFNNSTCYMYKTIISVSVVSVIVVSTVAFLIYHFYFHLILIAGCKKYSRGESIYDAFVIYSSQNEDWVRNELVKNLEEGVPRFHLCLHYRDFIPGVAIAANIIQEGFHKSRKVIVVVSRHFIQSRWCIFEYEIAQTWQFLSSRSGIIFIVLEKVEKSLLRQQVELYRLLSRNTYLEWEDNPLGRHIFWRRLKNALLDGKASNPEQTAEEEQETATWT ly96_mouse Lymphocyte antigen 96 Protein MD-2 ESOP-1 Ly96 Esop1 Md2 protein protein mouse Mus musculus Mouse MLPFILFSTLLSPILTESEKQQWFCNSSDAIISYSYCDHLKFPISISSEPCIRLRGTNGFVHVEFIPRGNLKYLYFNLFISVNSIELPKRKEVLCHGHDDDYSFCRALKGETVNTSIPFSFEGILFPKGHYRCVAEAIAGDTEEKLFCLNFTIIHRRDVN tlr4_human Toll-like receptor 4 TLR4 hToll protein protein human Homo sapiens Human MMSASRLAGTLIPAMAFLSCVRPESWEPCVEVVPNITYQCMELNFYKIPDNLPFSTKNLDLSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALGAFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHLDLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSLNVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRLAYLDYYLDDIIDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTSNKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLGLEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFNGIFNGLSSLEVLKMAGNSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPYKCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQNDFACTCEHQSFLQWIKDQRQLLVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVSVLSVLVVSVVAVLVYKFYFHLMLLAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAANIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLRQQVELYRLLSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGTVGTGCNWQEATSI eritoran tetrasodium Eritoran small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) Eritoran is an analog of lipopolysaccharide (LPS). tlr4_q4g1l2_protein TV3 Hybrid of human TLR4 and Hagfish VLR protein protein human Homo sapiens Human EPCVEVVPNITYQCMELNFYKIPDNLPFSTKNLDLSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALGAFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHLDLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLKELALDTNQLKSVPDGIFDRLTSLQKIWLHTNPWDCSCPRIDYLSRWLNKNSQKEQGSAKCSGSGKPVRSIICP An amino acid sequence which is not represented in UniProt ly96-tlr4_q4g1l2_tv8 hMD-2-TV8 complex dimerizes in the presence of LPS in a gel filtration chromatography assay 668162 N/A 668166 unspecified role unspecified role neutral component neutral component trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 N/A 668167 unspecified role unspecified role neutral component neutral component trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 physical association physical association false false false 6 A Lipolysaccharide (LPS) - The hMD-2-TV8 complex dimerizes in thepresence of LPS. MW = 150 kDa The hMD-2-TV8 complex does not dimerize in the presence of the LPS analog Eritoran. The central and/or C-terminal domains of TLR4 are required for the receptor dimerization because the TV3 hybrid that contains only the N-terminal domain and a part of the central domain interacts normally with MD-2 but did not form a heterotetramer after LPS binding ly96-tlr4-1 mMD-2-mTLR4 complex dimerizes in the presence of LPS in a gel filtration chromatography assay 668162 N/A 668168 unspecified role unspecified role neutral component neutral component trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 N/A 668169 unspecified role unspecified role neutral component neutral component trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 physical association physical association false false false 6 A Lipopolysaccharide (LPS) - The mMD-2-mTLR4 complex dimerizes in the presence of LPS. MW = 160 kDa The mMD-2-mTLR4 complex does not dimerize in the presence of the LPS analog Eritoran. ly96-tlr4-2 hMD-2-hTLR4 complex dimerizes in the presence of LPS in a gel filtration chromatography assay 668162 N/A 668170 unspecified role unspecified role neutral component neutral component trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 N/A 668166 unspecified role unspecified role neutral component neutral component trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 physical association physical association false false false 6 A MW = 160 kDa Lipopolysaccharide (LPS) - The hMD-2-hTLR4 complex dimerizes in the presence of LPS. The hMD-2-hTLR4 complex does not dimerize in the presence of the LPS analog Eritoran. ly96-tlr4-3 hMD-2-TV8 complex dimerizes in the presence of LPS in a Native PAGE assay 668163 N/A 668170 unspecified role unspecified role neutral component neutral component trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 N/A 668167 unspecified role unspecified role neutral component neutral component trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 physical association physical association false false false 6 B The central and/or C-terminal domains of TLR4 are required for the receptor dimerization because the TV3 hybrid that contains only the N-terminal domain and a part of the central domain interacts normally with MD-2 but did not form a heterotetramer after LPS binding. Lipopolysaccharide (LPS) - The hMD-2-TV8 complex dimerizes in the presence of LPS. The hMD-2-TV8 complex does not dimerize in the presence of the LPS analog Eritoran. ly96-tlr4-4 hMD-2-hTLR4 complex dimerizes in the presence of LPS in a native PAGE assay 668163 N/A 668166 unspecified role unspecified role neutral component neutral component Q9Y6Y9:p.His155Ala mutation disrupting mutation disrupting interaction mutation disrupting mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain false Q9Y6Y9:p.Phe126Ala mutation disrupting mutation disrupting interaction mutation disrupting mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain false trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 N/A 668170 unspecified role unspecified role neutral component neutral component trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 physical association physical association false false false 6 B Lipopolysaccharide (LPS) - The hMD-2-hTLR4 complex dimerizes in the presence of LPS. The hMD-2-hTLR4 complex does not dimerize in the presence of the LPS analog Eritoran. Phe126 and His155 mutants of MD-2 bound as normal to TLR4 and LPS, but their complex with TLR4 was not dimerized by LPS. Val82 and Met85 are located close to Phe126 and His155 but altering them by mutation did not affect multimerization. This confirms that the Phe126 and His155 residues play specific roles in receptor dimerization. ly96-tlr4-5 mMD-2-mTLR4 complex dimerizes in the presence of LPS in a native PAGE assay 668163 N/A 668168 unspecified role unspecified role neutral component neutral component trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 N/A 668169 unspecified role unspecified role neutral component neutral component trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 physical association physical association false false false 6 B Lipolysaccharide (LPS) - The mMD-2-mTLR4 complex dimerizes in the presence of LPS. The mMD-2-mTLR4 complex does not dimerize in the presence of the LPS analog Eritoran. ly96-tlr4 Crystal structure of mouse TLR4-MD-2 complex 668164 N/A 668168 unspecified role unspecified role neutral component neutral component region ectodomain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false spofr Spodoptera frugiperda (Fall armyworm) Fall armyworm Stoichiometry: 1.0 N/A 668169 unspecified role unspecified role neutral component neutral component spofr Spodoptera frugiperda (Fall armyworm) Fall armyworm Stoichiometry: 1.0 direct interaction direct interaction false false false 1, Table S5 2.8 A Rsym or Rmerge = 0.095 (0.31) (Highest resolution shell is shown in parenthesis. A.U. Asymmetric Units) ly96-tlr4_q4g1l2 Crystal structure of TV3M (human TLR4 and hagfish VLR hybrid) and hMD2 and Eritoran 668164 N/A 668166 unspecified role unspecified role neutral component neutral component spofr Spodoptera frugiperda (Fall armyworm) Fall armyworm Stoichiometry: 2.0 N/A 668171 unspecified role unspecified role neutral component neutral component N/A 668172 unspecified role unspecified role neutral component neutral component spofr Spodoptera frugiperda (Fall armyworm) Fall armyworm Stoichiometry: 2.0 direct interaction direct interaction false false false 5, Table S5 2.8 A Rsym or Rmerge = 0.089 (0.38) (Highest resolution shell is shown in parenthesis. A.U. Asymmetric Units) ly96-tlr4-6 hMD-2-hTLR4 complex dimerizes in the presence of LPS in a cross-linking assay 668165 N/A 668170 unspecified role unspecified role neutral component neutral component region ectodomain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 N/A 668166 unspecified role unspecified role neutral component neutral component trini-high_5 Trichoplusia ni cell line from eggs high_5 Insect cell line from Trichoplusia ni egg cells Invitrogen supplies this cell line. Invitrogen supply this cell line. Stoichiometry: 2.0 physical association physical association false false false 6 C Lipolysaccharide (LPS) - The hMD-2-hTLR4 complex dimerizes in the presence of LPS. MW = 175 kDa