8G6I: Coagulation factor VIII

Coagulation factor VIII bound to a patient-derived anti-C1 domain antibody inhibitor. Determined by electron microscopy at 4.23 Å resolution. Released 24 May 2023.

Method: Electron microscopy
Resolution: 4.23 Å
Organisms: Sus scrofa, Homo sapiens
Chains: 3
Atoms: 13,287
Mol. weight: 215.05 kDa
Released: 24 May 2023

Explore 8G6I in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8G6I contains 35 α-helices and 97 β-strands across 3 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: 21 helices, 75 β-strands

Element	Residues	Length	Sheet
β-strand	3-9	7	1
β-strand	10-11	2	2
β-strand	50-51	2	2
α-helix	64-67	4
β-strand	78-80	3	3
β-strand	84-91	8	1
β-strand	139-140	2	1
β-strand	157-159	3	4
α-helix	166-171	6
β-strand	175-177	3	4
β-strand	178-180	3	3
β-strand	198	1	5
β-strand	201-203	3	6
β-strand	232-234	3	6
β-strand	235	1	7
β-strand	238	1	7
β-strand	247-248	2	8
β-strand	252	1	9
β-strand	258	1	5
β-strand	259-260	2	10
β-strand	279	1	11
β-strand	282	1	11
β-strand	293-294	2	10
β-strand	301	1	9
β-strand	326-327	2	8
α-helix	408-410	3
β-strand	453	1	12
α-helix	517-519	3
β-strand	528	1	13
β-strand	533-534	2	14
α-helix	539-545	7
β-strand	548-549	2	14
β-strand	551	1	12
β-strand	554	1	13
β-strand	576	1	15
β-strand	579	1	16
α-helix	587-594	8
α-helix	598-600	3
α-helix	606-612	7
β-strand	614	1	16
β-strand	617	1	15
β-strand	637	1	17
β-strand	649-650	2	18
β-strand	659	1	19
β-strand	664	1	19
β-strand	669-670	2	18
β-strand	678	1	17
α-helix	1694-1697	4
β-strand	1701-1706	6	20
β-strand	1731-1736	6	20
α-helix	1751-1753	3
β-strand	1765	1	21
β-strand	1773-1774	2	22
β-strand	1814-1815	2	22
α-helix	1818-1820	3
α-helix	1821-1823	3
β-strand	1833	1	21
β-strand	1836-1837	2	23
α-helix	1843-1847	5
β-strand	1853-1854	2	23
β-strand	1857	1	21
β-strand	1877-1878	2	24
α-helix	1914-1916	3
β-strand	1933-1934	2	25
β-strand	1940-1944	5	24
α-helix	1950-1952	3
β-strand	1958	1	26
β-strand	1963-1964	2	24
β-strand	1985-1988	4	24
β-strand	1998	1	26
α-helix	2003-2006	4
β-strand	2015-2016	2	25
β-strand	2023	1	27
α-helix	2048-2050	3
β-strand	2071-2074	4	28
β-strand	2080-2085	6	27
β-strand	2089-2091	3	29
β-strand	2094-2096	3	29
β-strand	2100-2106	7	28
β-strand	2113-2114	2	28
β-strand	2126-2127	2	28
α-helix	2143	1
β-strand	2144-2145	2	27
β-strand	2148-2155	8	28
β-strand	2165-2169	5	27
α-helix	2187-2189	3
α-helix	2205-2207	3
β-strand	2209	1	30
β-strand	2219	1	31
β-strand	2244-2246	3	30
β-strand	2260-2265	6	32
α-helix	2280-2281	2
β-strand	2293-2294	2	30
β-strand	2305-2310	6	32
β-strand	2319	1	31
β-strand	2320-2321	2	30

Chain B: 9 helices, 17 β-strands

Element	Residues	Length	Sheet
β-strand	2-3	2	33
β-strand	7	1	34
β-strand	20-21	2	35
β-strand	22	1	34
β-strand	33-34	2	36
β-strand	36-37	2	37
β-strand	38	1	38
β-strand	45-46	2	37
β-strand	49	1	39
β-strand	53	1	39
α-helix	54-55	2
β-strand	62-67	6	35
β-strand	70-75	6	35
β-strand	85	1	38
β-strand	89-90	2	36
β-strand	96-97	2	33
α-helix	112-113	2
β-strand	114	1	40
α-helix	115	1
α-helix	119-121	3
α-helix	122-127	6
α-helix	135-136	2
β-strand	137	1	40
α-helix	145-147	3
α-helix	165-167	3
α-helix	183-188	6

Chain C: 5 helices, 5 β-strands

Element	Residues	Length	Sheet
β-strand	5-6	2	41
β-strand	22-23	2	41
β-strand	77	1	41
α-helix	87-90	4
α-helix	129-131	3
α-helix	132-135	4
α-helix	173-174	2
β-strand	175	1	42
β-strand	180	1	42
α-helix	190-193	4

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Coagulation factor VIII chimera from human and pig	A	protein	1467	Sus scrofa, Homo sapiens	P00451 (AlphaFold model), P12263 (AlphaFold model)
NB33 light chain	B	protein	211	Homo sapiens
NB33 heavy chain	C	protein	215	Homo sapiens

Sequence of entity 1 (A), FASTA

>8G6I_1 Coagulation factor VIII chimera from human and pig (chains A)
MQLELSTCVFLCLLPLGFSAIRRYYLGAVELSWDYRQSELLRELHVDTRFPATAPGALPL
GPSVLYKKTVFVEFTDQLFSVARPRPPWMGLLGPTIQAEVYDTVVVTLKNMASHPVSLHA
VGVSFWKSSEGAEYEDHTSQREKEDDKVLPGKSQTYVWQVLKENGPTASDPPCLTYSYLS
HVDLVKDLNSGLIGALLVCREGSLTRERTQNLHEFVLLFAVFDEGKSWHSARNDSWTRAM
DPAPARAQPAMHTVNGYVNRSLPGLIGCHKKSVYWHVIGMGTSPEVHSIFLEGHTFLVRH
HRQASLEISPLTFLTAQTFLMDLGQFLLFCHISSHHHGGMEAHVRVESCAEEPQLRRKAD
EEEDYDDNLYDSDMDVVRLDGDDVSPFIQIRSVAKKHPKTWVHYIAAEEEDWDYAPLVLA
PDDRSYKSQYLNNGPQRIGRKYKKVRFMAYTDETFKTREAIQHESGILGPLLYGEVGDTL
LIIFKNQASRPYNIYPHGITDVRPLYSRRLPKGVKHLKDFPILPGEIFKYKWTVTVEDGP
TKSDPRCLTRYYSSFVNMERDLASGLIGPLLICYKESVDQRGNQIMSDKRNVILFSVFDE
NRSWYLTENIQRFLPNPAGVQLEDPEFQASNIMHSINGYVFDSLQLSVCLHEVAYWYILS
IGAQTDFLSVFFSGYTFKHKMVYEDTLTLFPFSGETVFMSMENPGLWILGCHNSDFRNRG
MTALLKVSSCDKNTGDYYEDSYEDISAYLLSKNNAIEPRSFAQNSRPPSASAPKPPVLRR
HQRDISLPTFQPEEDKMDYDDIFSTETKGEDFDIYGEDENQDPRSFQKRTRHYFIAAVEQ
LWDYGMSESPRALRNRAQNGEVPRFKKVVFREFADGSFTQPSYRGELNKHLGLLGPYIRA
EVEDNIMVTFKNQASRPYSFYSSLISYPDDQEQGAEPRHNFVQPNETRTYFWKVQHHMAP
TEDEFDCKAWAYFSDVDLEKDVHSGLIGPLLICRANTLNAAHGRQVTVQEFALFFTIFDE
TKSWYFTENVERNCRAPCHLQMEDPTLKENYRFHAINGYVMDTLPGLVMAQNQRIRWYLL
SMGSNENIHSIHFSGHVFSVRKKEEYKMAVYNLYPGVFETVEMLPSKVGIWRIECLIGEH
LQAGMSTTFLVYSKKCQTPLGMASGHIRDFQITASGQYGQWAPKLARLHYSGSINAWSTK
EPFSWIKVDLLAPMIIHGIKTQGARQKFSSLYISQFIIMYSLDGKKWQTYRGNSTGTLMV
FFGNVDSSGIKHNIFNPPIIARYIRLHPTHYSIRSTLRMELMGCDLNSCSMPLGMESKAI
SDAQITASSYFTNMFATWSPSKARLHLQGRSNAWRPQVNNPKEWLQVDFQKTMKVTGVTT
QGVKSLLTSMYVKEFLISSSQDGHQWTLFFQNGKVKVFQGNQDSFTPVVNSLDPPLLTRY
LRIHPQSWVHQIALRMEVLGCEAQDLY

Sequence of entity 2 (B), FASTA

>8G6I_2 NB33 light chain (chains B)
DIQMTQSPSSLSASVGDTVTIACRASRDIRNDLAWYQQKPGKAPKLLIYATSRLQSGVPS
RFSGSGSFTDFTLTINSLQPDDSATYYCLQDSDYPLTFGGGTKVDIKGTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNR

Sequence of entity 3 (C), FASTA

>8G6I_3 NB33 heavy chain (chains C)
EVQLVESGGGVVQPGRSLRLSCVDSGLTFSSYGMHWVRQAPGAGLEWVAVISYDGNDKYY
ADSVKGRFAISRDNAKNTLYLQMNSLTIEDTAVYYCAKDLIESNIAEAFWGQGTLVTVSS
KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTATYTCNVDHKPSNTKVDKRV

Primary citation

Structure of coagulation factor VIII bound to a patient-derived anti-C1 domain antibody inhibitor. Childers, K.C., Avery, N.G., Estrada Alamo, K.A. et al. Blood (2023) 142:197-201. DOI 10.1182/blood.2023020181 · PubMed

Other PDB entries of the same protein (UniProt P00451 (AlphaFold model), which also has an AlphaFold model), best resolution first:

3HNY 1.07 Å, Factor VIII Trp2313-His2315 segment is involved in membrane binding as shown by crystal…
3HNB 1.15 Å, Factor VIII Trp2313-His2315 segment is involved in membrane binding as shown by crystal…
1D7P 1.5 Å, Crystal structure of the c2 domain of human factor viii at 1.5 a resolution at 1.5 A
9D5D 1.83 Å, Crystal Structure of Blood Coagulation Factor VIII C2 Domain Mutant L2251A/L2252A
1IQD 2.0 Å, Human Factor VIII C2 Domain complexed to human monoclonal BO2C11 Fab.
3HOB 2.07 Å, Factor VIII Trp2313-His2315 segment is involved in membrane binding as shown by crystal…
4PT6 2.1 Å, The discobody: an engineered discoidin domain from factor VIII that binds v 3 integrin…
4KI5 2.47 Å, Cystal structure of human factor VIII C2 domain in a ternary complex with murine…
4XZU 2.61 Å, Crystal Structure of the Human Factor VIII C2 Domain in Complex with Murine 3E6…
7KWO 2.9 Å, Rfviiifc-vwf-xten (BIVV001)
36JL 3.15 Å, Coagulation factor VIII, full-length, membrane-bound, on Ptd-choline : Ptd-serine 75:25…
9JBV 3.17 Å, Structure of Engineered Coagulation Factor VIII with Enhanced Secretion and Coagulation…

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