6WOL: Next generation monomeric IgG4 Fc

Next generation monomeric IgG4 Fc bound to neonatal Fc receptor. Determined by X-ray diffraction at 2.49 Å resolution. Released 15 Sept 2021.

Method: X-ray diffraction
Resolution: 2.49 Å
Organism: Homo sapiens
Chains: 3
Atoms: 4,708
Mol. weight: 66.69 kDa
Released: 15 Sept 2021

Explore 6WOL in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6WOL contains 22 α-helices and 51 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: 9 helices, 19 β-strands

Element	Residues	Length	Sheet
β-strand	6-14	9	6
α-helix	17-18	2
β-strand	24-30	7	6
β-strand	33-39	7	6
β-strand	46-47	2	6
α-helix	49-53	5
α-helix	60-80	21
β-strand	89-99	11	6
β-strand	103-112	10	6
β-strand	115-121	7	6
β-strand	126-129	4	6
α-helix	132-142	11
α-helix	147-153	7
α-helix	154-158	5
α-helix	159-169	11
β-strand	178	1	7
α-helix	179-180	2
β-strand	181-188	8	8
β-strand	193-203	11	8
β-strand	204	1	7
β-strand	208-214	7	9
β-strand	217-220	4	9
β-strand	223	1	8
β-strand	226-228	3	8
β-strand	234-243	10	8
α-helix	247-249	3
β-strand	250-256	7	9
β-strand	263-265	3	9

Chain B: 2 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3	1	10
α-helix	4-5	2
β-strand	6-11	6	11
β-strand	21-30	10	11
β-strand	31	1	10
β-strand	36-41	6	12
β-strand	44-45	2	12
α-helix	46	1
β-strand	50-51	2	11
β-strand	55-56	2	11
β-strand	62-70	9	11
β-strand	78-83	6	12
β-strand	91-94	4	12

Chain H: 11 helices, 21 β-strands

Element	Residues	Length	Sheet
β-strand	239-243	5	1
α-helix	244-246	3
α-helix	247-251	5
β-strand	258-266	9	1
β-strand	274-279	6	2
β-strand	282-284	3	2
β-strand	288-289	2	1
α-helix	290-292	3
β-strand	293-294	2	1
α-helix	295	1
β-strand	300-307	8	1
α-helix	310-314	5
β-strand	318-324	7	2
β-strand	332-337	6	2
α-helix	338-340	3
β-strand	344	1	3
α-helix	345-346	2
β-strand	347-351	5	4
α-helix	352-354	3
β-strand	362-372	11	4
β-strand	373	1	3
β-strand	378-383	6	5
β-strand	386-387	2	5
β-strand	391-393	3	4
α-helix	394-396	3
β-strand	397-398	2	4
β-strand	404-413	10	4
α-helix	414-418	5
β-strand	423-428	6	5
α-helix	433-435	3
β-strand	436	1	5
β-strand	442	1	5

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Immunoglobulin heavy constant gamma 4	H	protein	209	Homo sapiens	P01861 (AlphaFold model)
IgG receptor FcRn large subunit p51	A	protein	267	Homo sapiens	P55899 (AlphaFold model)
Beta-2-microglobulin	B	protein	99	Homo sapiens	P61769 (AlphaFold model)

Sequence of entity 1 (H), FASTA

>6WOL_1 Immunoglobulin heavy constant gamma 4 (chains H)
GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTFPPEQE
EMTKNQVSLRCLVKGFYPSDIAVEWESNGQPENNYKTTKPVLDSDGSFRLESRLTVDKSR
WQEGNVFSCSVMHEACSYHLCKSLSLSLG

Sequence of entity 2 (A), FASTA

>6WOL_2 IgG receptor FcRn large subunit p51 (chains A)
AESHLSLLYHLTAVSSPAPGTPAFWVSGWLGPQQYLSYNSLRGEAEPCGAWVWENQVSWY
WEKETTDLRIKEKLFLEAFKALGGKGPYTLQGLLGCELGPDNTSVPTAKFALNGEEFMNF
DLKQGTWGGDWPEALAISQRWQQQDKAANKELTFLLFSCPHRLREHLERGRGNLEWKEPP
SMRLKARPSSPGFSVLTCSAFSFYPPELQLRFLRNGLAAGTGQGDFGPNSDGSFHASSSL
TVKSGDEHHYCCIVQHAGLAQPLRVEL

Sequence of entity 3 (B), FASTA

>6WOL_3 Beta-2-microglobulin (chains B)
IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

Primary citation

In vivo pharmacokinetic enhancement of monomeric Fc and monovalent bispecific designs through structural guidance. Shan, L., Dyk, N.V., Haskins, N. et al. Commun Biol (2021) 4:1048-1048. DOI 10.1038/s42003-021-02565-5 · PubMed

Other PDB entries of the same protein (UniProt P01861 (AlphaFold model), which also has an AlphaFold model), best resolution first:

3EO0 1.75 Å, Structure of the Transforming Growth Factor-Beta Neutralizing Antibody GC-1008
4B53 1.8 Å, Crystal structure of the isolated IgG4 CH3 domain
5W5N 1.85 Å, Crystal structure of human IgG4-Sigma2 Fc fragment
4C54 1.9 Å, Crystal structure of recombinant human IgG4 Fc
5W5M 1.9 Å, Crystal structure of human IgG4-Sigma1 Fc fragment
5HVW 1.95 Å, Monomeric IgG4 Fc
3X3F 2.1 Å, TRAIL-R2 Extracellular Region Complexed to a Fab fragment from Human Agonist Antibody…
6WMH 2.3 Å, Next generation monomeric IgG4 Fc
4C55 2.35 Å, Crystal structure of serum-derived human IgG4 Fc
6WNA 2.4 Å, Next generation monomeric IgG4 Fc
3X3G 2.51 Å, Fab fragment from anti TRAIL-R2 Human Agonist Antibody KMTR2
6WIB 2.55 Å, Next generation monomeric IgG4 Fc

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