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6WNA

Non-classical MHC Class I molecule Feonatal Fc receptor (FcRn) with Ig heavy chain gamma at 2.40Å 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 beta2m and ig heavy chain gamma

1. Beta 2 microglobulin
['B']
2. Fc receptor (FcRn)
['A']
3. ig_heavy_chain_gamma
['H']

Species

Locus / Allele group

Non-classical MHC Class I molecule

Publication

In vivo pharmacokinetic enhancement of monomeric Fc and monovalent bispecific designs through structural guidance.

Shan L, Dyk NV, Haskins N, Cook KM, Rosenthal KL, Mazor R, Dragulin-Otto S, Jiang Y, Wu H, Dall'Acqua WF, Borrok MJ, Damschroder MM, Oganesyan V
Commun Biol (2021) 4, 1048 [doi:10.1038/s42003-021-02565-5]  [pubmed:34497355] 

In a biologic therapeutic landscape that requires versatility in targeting specificity, valency and half-life modulation, the monomeric Fc fusion platform holds exciting potential for the creation of a class of monovalent protein therapeutics that includes fusion proteins and bispecific targeting molecules. Here we report a structure-guided approach to engineer monomeric Fc molecules to adapt multiple versions of half-life extension modifications. Co-crystal structures of these monomeric Fc variants with Fc neonatal receptor (FcRn) shed light into the binding interactions that could serve as a guide for engineering the half-life of antibody Fc fragments. These engineered monomeric Fc molecules also enabled the generation of a novel monovalent bispecific molecular design, which translated the FcRn binding enhancement to improvement of in vivo serum half-life.

Structure deposition and release

Deposited: 2020-04-22
Released: 2021-09-15
Revised: 2021-09-22

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication

Chain sequences

1. Beta 2 microglobulin
Beta 2 microglobulin
        10        20        30        40        50        60
IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW
        70        80        90
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM
2. Fc receptor (FcRn)
Fc receptor (FcRn)
        10        20        30        40        50        60
HLSLLYHLTAVSSPAPGTPAFWVSGWLGPQQYLSYNSLRGEAEPCGAWVWENQVSWYWEK
        70        80        90       100       110       120
ETTDLRIKEKLFLEAFKALGGKGPYTLQGLLGCELGPDNTSVPTAKFALNGEEFMNFDLK
       130       140       150       160       170       180
QGTWGGDWPEALAISQRWQQQDKAANKELTFLLFSCPHRLREHLERGRGNLEWKEPPSMR
       190       200       210       220       230       240
LKARPSSPGFSVLTCSAFSFYPPELQLRFLRNGLAAGTGQGDFGPNSDGSFHASSSLTVK
       250       260
SGDEHHYCCIVQHAGLAQPLRVEL
3. ig_heavy_chain_gamma
ig_heavy_chain_gamma
        10        20        30        40        50        60
PSVFLFPPKPKDTLYITREPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN
        70        80        90       100       110       120
STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTFPPEQEE
       130       140       150       160       170       180
MTKNQVSLRCLVKGFYPSDIAVEWESNGQPENNYKTTKPVLDSDGSFRLESRLTVDKSRW
       190       200
QEGNVFSCSVMHEALHNHYTQKSLSLS

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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or in the case of JSON formatted files to retrieve it and use it as part of notebooks such as Jupyter or GoogleColab.
Please take note of the data license. Using data from this site assumes that you have read and will comply with the license.

Complete structures

Aligned structures [cif]
  1. 6WNA assembly 1  

Components

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

Derived data

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

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.