 |
PDBsum entry 6ddr
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
6ddr
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
214 a.a.
|
|
|
|
|
|
|
|
|
|
|
221 a.a.
|
|
|
|
|
|
|
|
|
|
|
94 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Immune system
|
|
|
Title:
|
|
Crystal structure analysis of the epitope of an anti-mica antibody
|
|
Structure:
|
|
Anti-mica fab fragment light chain clone 13a9. Chain: a. Engineered: yes. Anti-mica fab fragment heavy chain clone 13a9. Chain: b. Engineered: yes. Mhc class i polypeptide-related sequence a. Chain: c. Synonym: mhc class i polypeptide-related sequence a,isoform cra_c,
|
|
Source:
|
|
Mus musculus. Organism_taxid: 10090. Strain: balb/c. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606. Gene: mica, hcg_2001511.
|
|
Resolution:
|
|
|
1.90Å
|
R-factor:
|
0.210
|
R-free:
|
0.247
|
|
|
Authors:
|
|
M.L.Matsumoto
|
|
Key ref:
|
|
T.N.Lombana
et al.
(2019).
High-resolution glycosylation site-engineering method identifies MICA epitope critical for shedding inhibition activity of anti-MICA antibodies.
MAbs,
11,
75-93.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
10-May-18
|
Release date:
|
24-Oct-18
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
No UniProt id for this chain
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
MAbs
11:75-93
(2019)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
High-resolution glycosylation site-engineering method identifies MICA epitope critical for shedding inhibition activity of anti-MICA antibodies.
|
|
T.N.Lombana,
M.L.Matsumoto,
A.M.Berkley,
E.Toy,
R.Cook,
Y.Gan,
C.Du,
P.Schnier,
W.Sandoval,
Z.Ye,
J.M.Schartner,
J.Kim,
C.Spiess.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
As an immune evasion strategy, MICA and MICB, the major histocompatibility
complex class I homologs, are proteolytically cleaved from the surface of cancer
cells leading to impairment of CD8 + T cell- and natural killer cell-mediated
immune responses. Antibodies that inhibit MICA/B shedding from tumors have
therapeutic potential, but the optimal epitopes are unknown. Therefore, we
developed a high-resolution, high-throughput glycosylation-engineered epitope
mapping (GEM) method, which utilizes site-specific insertion of N-linked glycans
onto the antigen surface to mask local regions. We apply GEM to the discovery of
epitopes important for shedding inhibition of MICA/B and validate the epitopes
at the residue level by alanine scanning and X-ray crystallography (Protein Data
Bank accession numbers 6DDM (1D5 Fab-MICA*008), 6DDR (13A9 Fab-MICA*008), 6DDV
(6E1 Fab-MICA*008). Furthermore, we show that potent inhibition of MICA shedding
can be achieved by antibodies that bind GEM epitopes adjacent to previously
reported cleavage sites, and that these anti-MICA/B antibodies can prevent tumor
growth in vivo.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
| |
Links
