8TY1: Coagulation factor VIII

Cryo-EM structure of coagulation factor VIII bound to NB2E9. Determined by electron microscopy at 3.46 Å resolution. Released 13 Sept 2023.

Method: Electron microscopy
Resolution: 3.46 Å
Organisms: Sus scrofa, Homo sapiens
Chains: 3
Atoms: 13,508
Mol. weight: 219.42 kDa
Released: 13 Sept 2023

Explore 8TY1 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8TY1 contains 36 α-helices and 142 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: 26 helices, 105 β-strands

Element	Residues	Length	Sheet
β-strand	3-5	3	1
β-strand	6-13	8	2
β-strand	48-55	8	2
β-strand	63	1	2
β-strand	76-77	2	3
β-strand	85-87	3	1
β-strand	90-91	2	2
α-helix	121-123	3
α-helix	125-127	3
β-strand	132	1	2
β-strand	137-139	3	1
β-strand	154-157	4	3
α-helix	165-170	6
β-strand	176-180	5	3
α-helix	192-195	4
β-strand	197-198	2	4
β-strand	200-203	4	5
β-strand	232-235	4	5
β-strand	238	1	5
β-strand	246-248	3	6
β-strand	253-259	7	4
β-strand	261	1	5
β-strand	270-272	3	6
β-strand	279	1	7
β-strand	282	1	7
β-strand	287	1	6
β-strand	294-300	7	4
β-strand	305-311	7	6
β-strand	323-327	5	6
β-strand	380	1	8
β-strand	383-394	12	9
α-helix	409-412	4
β-strand	415	1	10
β-strand	418	1	10
β-strand	422-429	8	9
β-strand	431	1	11
α-helix	438	1
β-strand	439	1	11
α-helix	440	1
α-helix	442-443	2
β-strand	459	1	8
β-strand	462-467	6	9
β-strand	476-477	2	12
β-strand	482-485	4	9
β-strand	508-514	7	9
β-strand	529-534	6	12
α-helix	539-545	7
β-strand	549-553	5	12
α-helix	572-573	2
β-strand	574-575	2	13
β-strand	576-580	5	14
α-helix	587-594	8
α-helix	606-612	7
β-strand	613-617	5	14
β-strand	620	1	14
β-strand	635-640	6	13
β-strand	652	1	15
β-strand	658-659	2	13
β-strand	664-665	2	13
β-strand	667	1	15
β-strand	675-680	6	13
β-strand	689	1	16
α-helix	695-699	5
β-strand	705	1	16
β-strand	1695-1697	3	17
β-strand	1701-1707	7	18
β-strand	1730-1736	7	18
α-helix	1751-1754	4
β-strand	1763-1765	3	19
β-strand	1770-1772	3	17
β-strand	1776	1	20
β-strand	1783	1	21
β-strand	1807	1	21
α-helix	1808	1
β-strand	1812	1	20
β-strand	1817-1818	2	17
α-helix	1821-1823	3
α-helix	1825-1826	2
β-strand	1832-1838	7	19
α-helix	1840-1842	3
α-helix	1843-1846	4
β-strand	1852-1858	7	19
β-strand	1874-1884	11	22
α-helix	1885-1887	3
α-helix	1892-1894	3
α-helix	1913-1916	4
β-strand	1917-1921	5	22
β-strand	1924	1	22
β-strand	1933-1935	3	23
β-strand	1940-1946	7	22
β-strand	1956-1958	3	24
β-strand	1963-1965	3	25
β-strand	1971-1973	3	25
β-strand	1975-1976	2	24
β-strand	1983-1987	5	22
β-strand	1994-1995	2	23
β-strand	1998-1999	2	24
α-helix	2003-2006	4
β-strand	2015-2017	3	23
β-strand	2024	1	26
β-strand	2038	1	26
α-helix	2048-2050	3
β-strand	2062-2064	3	27
β-strand	2071-2087	17	26
β-strand	2089-2091	3	28
β-strand	2094-2096	3	28
β-strand	2097-2106	10	26
β-strand	2113-2114	2	26
β-strand	2126-2127	2	26
β-strand	2144-2157	14	26
β-strand	2160-2162	3	27
β-strand	2163-2169	7	26
α-helix	2187-2189	3
β-strand	2191-2192	2	29
β-strand	2197	1	30
β-strand	2202	1	30
α-helix	2205-2207	3
β-strand	2209	1	31
β-strand	2230-2233	4	29
β-strand	2239-2246	8	31
β-strand	2248-2250	3	32
β-strand	2253-2255	3	32
β-strand	2256-2257	2	33
β-strand	2260-2265	6	29
β-strand	2272-2273	2	29
β-strand	2276	1	34
β-strand	2279	1	34
β-strand	2293-2296	4	31
β-strand	2305-2310	6	29
β-strand	2313-2314	2	33
β-strand	2320-2326	7	31

Chain B: 5 helices, 16 β-strands

Element	Residues	Length	Sheet
β-strand	5-7	3	35
β-strand	10-12	3	36
β-strand	19-29	11	35
α-helix	31-33	3
β-strand	34-39	6	36
β-strand	45-50	6	36
β-strand	54-55	2	36
β-strand	63-76	14	35
β-strand	86-91	6	36
α-helix	94-96	3
β-strand	99-100	2	36
β-strand	104-107	4	36
β-strand	116-120	5	37
α-helix	124-129	6
β-strand	135-139	5	37
β-strand	150-151	2	38
β-strand	156-157	2	38
β-strand	161-165	5	37
α-helix	166-169	4
β-strand	176-181	6	37
α-helix	185-190	6

Chain C: 5 helices, 21 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	39
β-strand	10-12	3	40
β-strand	18-25	8	39
β-strand	40-49	10	40
β-strand	56-61	6	40
β-strand	68-70	3	40
α-helix	72-74	3
β-strand	78-82	5	39
β-strand	88-93	6	39
α-helix	98-100	3
β-strand	102-109	8	40
β-strand	124-127	4	40
β-strand	131-135	5	40
β-strand	141	1	41
β-strand	144-148	5	42
α-helix	152-154	3
β-strand	162-169	8	42
β-strand	170	1	41
β-strand	174-177	4	43
α-helix	179-181	3
β-strand	187-189	3	42
α-helix	190-192	3
β-strand	193-194	2	42
β-strand	200-206	7	42
β-strand	219-224	6	43
β-strand	229-234	6	43

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Coagulation factor VIII	A	protein	1467	Sus scrofa, Homo sapiens	P00451 (AlphaFold model), P12263 (AlphaFold model)
NB2E9 light chain	B	protein	216	Homo sapiens
NB2E9 heavy chain	C	protein	235	Homo sapiens

Sequence of entity 1 (A), FASTA

>8TY1_1 Coagulation factor VIII (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

>8TY1_2 NB2E9 light chain (chains B)
EIVLTQFPGTLSLSPGERATLSCRASQSVASAYLAWYQQKPGQAPRLLIYGASSRATDIP
HRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGTSALLTFGGGTKVEIKRTVAAPSVFIF
PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST
LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

Sequence of entity 3 (C), FASTA

>8TY1_3 NB2E9 heavy chain (chains C)
QVQLVQSGAEVKKPGASVKVSCKTSGYNFTGYSASGHIFTAYSVHWVRQAPGQGLEWMGR
INPNSGATDYAHKFQGRVTMSRDTSISTAYMELSRLTSDDTAMYYCARADNYFDIVTGYT
SHYFDYWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS
GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRV

Primary citation

Structural basis for inhibition of coagulation factor VIII reveals a shared antigenic hotspot on the C1 domain. Childers, K.C., Cowper, B., Vaughan, J.D. et al. J Thromb Haemost (2024) 22:2449-2459. DOI 10.1016/j.jtha.2024.05.024 · 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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