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6NHA

Non-classical MHC Class I molecule Feonatal Fc receptor (FcRn) with antibody at 2.38Å resolution

Data provenance

Structure downloaded from PDB Europe using the Coordinate Server. Aligned to residues 1-180 of 1HHK2 using the CEALIGN3 function of PyMol4. Chain assigment using a Levenshtein distance5 method using data from the PDBe REST API6. Organism data from PDBe REST API. Data for both of these operations from the Molecules endpoint. Structure visualised with 3DMol7.

Information sections

Complex type

Fcrn with antibody

1. ab_heavy
['H']
2. ab_light
['L']
3. Beta 2 microglobulin
['B']
4. Fc receptor (FcRn)
['A']

Species

Locus / Allele group

Non-classical MHC Class I molecule

Publication

Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses.

Blumberg LJ, Humphries JE, Jones SD, Pearce LB, Holgate R, Hearn A, Cheung J, Mahmood A, Del Tito B, Graydon JS, Stolz LE, Bitonti A, Purohit S, de Graaf D, Kacena K, Andersen JT, Christianson GJ, Roopenian DC, Hubbard JJ, Gandhi AK, Lasseter K, Pyzik M, Blumberg RS
Sci Adv (2019) 5, eaax9586 [doi:10.1126/sciadv.aax9586]  [pubmed:31897428] 

The neonatal crystallizable fragment receptor (FcRn) functions as an intracellular protection receptor for immunoglobulin G (IgG). Recently, several clinical studies have reported the lowering of circulating monomeric IgG levels through FcRn blockade for the potential treatment of autoimmune diseases. Many autoimmune diseases, however, are derived from the effects of IgG immune complexes (ICs). We generated, characterized, and assessed the effects of SYNT001, a FcRn-blocking monoclonal antibody, in mice, nonhuman primates (NHPs), and humans. SYNT001 decreased all IgG subtypes and IgG ICs in the circulation of humans, as we show in a first-in-human phase 1, single ascending dose study. In addition, IgG IC induction of inflammatory pathways was dependent on FcRn and inhibited by SYNT001. These studies expand the role of FcRn in humans by showing that it controls not only IgG protection from catabolism but also inflammatory pathways associated with IgG ICs involved in a variety of autoimmune diseases.

Structure deposition and release

Deposited: 2018-12-21
Released: 2019-12-25
Revised: 2020-01-15

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication

Chain sequences

1. ab_heavy
ab_heavy
        10        20        30        40        50        60
QVQLVQSGAELKKPGASVKLSCKASGYTFTSYGISWVKQATGQGLEWIGEIYPRSGNTYY
        70        80        90       100       110       120
NEKFKGRATLTADKSTSTAYMELRSLRSEDSAVYFCARSTTVRPPGIWGTGTTVTVSSAS
       130       140       150       160       170       180
TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
       190       200       210
YSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKY
2. ab_light
ab_light
        10        20        30        40        50        60
DIQMTQSPSSLSASVGDRVTITCKASDHINNWLAWYQQKPGQAPRLLISGATSLETGVPS
        70        80        90       100       110       120
RFSGSGTGKDYTLTISSLQPEDFATYYCQQYWSTPYTFGGGTKVEIKRTVAAPSVFIFPP
       130       140       150       160       170       180
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
       190       200       210
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
3. Beta 2 microglobulin
Beta 2 microglobulin
        10        20        30        40        50        60
IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW
        70        80        90
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM
4. Fc receptor (FcRn)
Fc receptor (FcRn)
        10        20        30        40        50        60
AESHLSLLYHLTAVSSPAPGTPAFWVSGWLGPQQYLSYNSLRGEAEPCGAWVWENQVSWY
        70        80        90       100       110       120
WEKETTDLRIKEKLFLEAFKALGGKGPYTLQGLLGCELGPDATSVPTAKFALNGEEFMNF
       130       140       150       160       170       180
DLKQGTWGGDWPEALAISQRWQQQDKAANKELTFLLFSCPHRLREHLERGRGNLEWKEPP
       190       200       210       220       230       240
SMRLKARPSSPGFSVLTCSAFSFYPPELQLRFLRNGLAAGTGQGDFGPNSDGSFHASSSL
       250       260       270
TVKSGDEHHYCCIVQHAGLAQPLRVELESPAKSENLYFQ

Data provenance

Sequences are retrieved via the Uniprot method of the RSCB REST API. Sequences are then compared to those derived from the PDB file and matched against sequences retrieved from the IPD-IMGT/HLA database for human sequences, or the IPD-MHC database for other species. Mouse sequences are matched against FASTA files from Uniprot. Sequences for the mature extracellular protein (signal petide and cytoplasmic tail removed) are compared to identical length sequences from the datasources mentioned before using either exact matching or Levenshtein distance based matching.

Downloadable data

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Complete structures

Aligned structures [cif]
  1. 6NHA assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 6NHA assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 6NHA assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/6nha

Data license

The data above is made available under a Creative Commons CC-BY 4.0 license. This means you can copy, remix, transform, build upon and redistribute the material, but you must give appropriate credit, provide a link to the license, and indicate if changes were made.
If you use any data downloaded from this site in a publication, please cite 'https://www.histo.fyi/'. A preprint is in preparation.

Footnotes


Creative Commons Licence
This work is licensed under a Creative Commons Attribution 4.0 International License.