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6QIP

Non-classical MHC Class I molecule Feonatal Fc receptor (FcRn) with serum albumin at 2.45Å 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 serum albumin

1. Beta 2 microglobulin
['C']
2. Fc receptor (FcRn)
['B']
3. Serum Albumin
['A']

Species

Locus / Allele group

Non-classical MHC Class I molecule

Publication

Identification of Binding Sites on Human Serum Albumin for Somapacitan, a Long-Acting Growth Hormone Derivative.

Johansson E, Nielsen AD, Demuth H, Wiberg C, Schj��dt CB, Huang T, Chen J, Jensen S, Petersen J, Thygesen P
Biochemistry (2020) 59, 1410-1419 [doi:10.1021/acs.biochem.0c00019]  [pubmed:32208682] 

Somapacitan, a human growth hormone derivative that binds reversibly to albumin, was investigated for human serum albumin (HSA) and HSA domain binding. Isothermal titration calorimetry (ITC) binding profiles showed high-affinity binding (∼100-1000 nM) of one somapacitan molecule and low-affinity binding (∼1000-10000 nM) of one to two somapacitan molecules to HSA. The high-affinity site was identified in HSA domain III using size exclusion chromatography (SEC) and ITC. SEC studies showed that the neonatal Fc receptor shields one binding site for somapacitan, indicating its position in domain III. A crystal structure of somapacitan in complex with HSA optimized for neonatal Fc receptor binding, having four amino acid residue replacements, identified a low-affinity site in fatty acid-binding site 6 (domain II). Surface plasmon resonance (SPR) showed these replacements affect the kinetics of the high-affinity binding site. Furthermore, small-angle X-ray scattering and SPR brace two somapacitan-binding sites on HSA.

Structure deposition and release

Deposited: 2019-01-21
Released: 2020-02-05
Revised: 2020-04-22

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       100
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDMHHHHHH
2. Fc receptor (FcRn)
Fc receptor (FcRn)
        10        20        30        40        50        60
AESHLSLLYHLTAVSSPAPGTPAFWVSGWLGPQQYLSYNSLRGEAEPCGAWVWENQVSWY
        70        80        90       100       110       120
WEKETTDLRIKEKLFLEAFKALGGKGPYTLQGLLGCELGPDNTSVPTAKFALNGEEFMNF
       130       140       150       160       170       180
DLKQGTWGGDWPEALAISQRWQQQDKAANKELTFLLFSCPHRLREHLERGRGNLEWKEPP
       190       200       210       220       230       240
SMRLKARPSSPGFSVLTCSAFSFYPPELQLRFLRNGLAAGTGQGDFGPNSDGSFHASSSL
       250       260       270
TVKSGDEHHYCCIVQHAGLAQPLRVELESPAKSS
3. Serum Albumin
Serum Albumin
        10        20        30        40        50        60
DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAE
        70        80        90       100       110       120
NCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEV
       130       140       150       160       170       180
DVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLP
       190       200       210       220       230       240
KLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTK
       250       260       270       280       290       300
VHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPA
       310       320       330       340       350       360
DLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKC
       370       380       390       400       410       420
CAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQMSA
       430       440       450       460       470       480
PTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTES
       490       500       510       520       530       540
LVNRRPCFSALEVDETYVPKEFNAGTFTFHADICTLSEKERQIKKQTALVELVKHKPKAT
       550       560       570       580
KEQLKAAMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL

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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   e.g. load http://www.histo.fyi/structures/downloads/1hhk_1_peptide.cif
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. 6QIP assembly 1  

Components

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

Derived data

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

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.