 |
PDBsum entry 4z5r
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cytokine/immune system
|
PDB id
|
|
|
|
4z5r
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
(+ 2 more)
141 a.a.
|
|
|
|
|
|
|
|
|
|
|
(+ 1 more)
217 a.a.
|
|
|
|
|
|
|
|
|
|
|
(+ 1 more)
213 a.a.
|
|
|
|
|
|
|
|
|
|
|
110 a.a.
|
|
|
|
|
|
|
|
|
|
|
117 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Cytokine/immune system
|
|
|
Title:
|
|
Rontalizumab fab bound to interferon-a2
|
|
Structure:
|
|
Interferon alpha-2. Chain: d, e, f, g, h, i, x, n. Synonym: ifn-alpha-2,interferon alpha-a,leif a. Engineered: yes. Anti-ifn-a antibody rontalizumab light chain. Chain: j, l, v, p, r, t, y, a. Engineered: yes. Anti-ifn-a antibody rontalizumab heavy chain modules vh and ch1 (fab).
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: ifna2, ifna2a, ifna2b, ifna2c. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_taxid: 562. Expression_system_taxid: 562
|
|
Resolution:
|
|
|
3.00Å
|
R-factor:
|
0.223
|
R-free:
|
0.251
|
|
|
Authors:
|
|
C.Eigenbrot,B.Maurer,I.Bosanac
|
|
Key ref:
|
|
B.Maurer
et al.
(2015).
Structural basis of the broadly neutralizing anti-interferon-α antibody rontalizumab.
Protein Sci,
24,
1440-1450.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
02-Apr-15
|
Release date:
|
08-Jul-15
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P01563
(IFNA2_HUMAN) -
Interferon alpha-2 from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
188 a.a.
141 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
No UniProt id for this chain
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
No UniProt id for this chain
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Protein Sci
24:1440-1450
(2015)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structural basis of the broadly neutralizing anti-interferon-α antibody rontalizumab.
|
|
B.Maurer,
I.Bosanac,
S.Shia,
M.Kwong,
R.Corpuz,
R.Vandlen,
K.Schmidt,
C.Eigenbrot.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Interferons-alpha (IFN-α) are the expressed gene products comprising thirteen
type I interferons with protein pairwise sequence similarities in the 77-96%
range. Three other widely expressed human type I interferons, IFN-β, IFN-κ and
IFN-ω have sequences 29-33%, 29-32% and 56-60% similar to the IFN-αs,
respectively. Type I interferons act on immune cells by producing subtly
different immune-modulatory effects upon binding to the extracellular domains of
a heterodimeric cell-surface receptor composed of IFNAR1 and IFNAR2, most
notably anti-viral effects. IFN-α has been used to treat infection by
hepatitis-virus type C (HCV) and a correlation between hyperactivity of
IFN-α-induced signaling and systemic lupus erythematosis (SLE), or lupus, has
been noted. Anti-IFN-α antibodies including rontalizumab have been under
clinical study for the treatment of lupus. To better understand the rontalizumab
mechanism of action and specificity, we determined the X-ray crystal structure
of the Fab fragment of rontalizumab bound to human IFN-α2 at 3Å resolution and
find substantial overlap of the antibody and IFNA2 epitopes on IFN-α2.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
| | |
Links
