 |
PDBsum entry 1fcc
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Complex (antibody/antigen)
|
PDB id
|
|
|
|
1fcc
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structure of the c2 fragment of streptococcal protein g in complex with the fc domain of human igg.
|
|
|
Authors
|
|
A.E.Sauer-Eriksson,
G.J.Kleywegt,
M.Uhlén,
T.A.Jones.
|
|
|
Ref.
|
|
Structure, 1995,
3,
265-278.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
BACKGROUND: Streptococcal protein G comprises two or three domains that bind to
the constant Fc region of most mammalian immunoglobulin Gs (IgGs). Protein G is
functionally related to staphylococcal protein A, with which it shares neither
sequence nor structural homology. RESULTS: To understand the competitive binding
of these two proteins to the Fc region, the crystal structure of a single
Ig-binding domain of streptococcal protein G was determined at 3.5 A resolution
in complex with the Fc fragment of human IgG and compared with the structures of
protein A:Fc and protein G:Fab complexes. Protein G binds to the interface
between the second and third heavy chain constant domains of Fc, which is
roughly the same binding site used by protein A. Protein G comprises one
alpha-helix packed onto a four-stranded beta-sheet. Residues from protein G that
are involved in binding are situated within the C-terminal part of the
alpha-helix, the N-terminal part of the third beta-strand and the loop region
connecting these two structural elements. The identified Fc-binding region of
protein G agrees well with both biochemical and NMR spectroscopic data. However,
the Fc-binding helices of protein G and protein A are not superimposable.
CONCLUSIONS: Protein G and protein A have developed different strategies for
binding to Fc. The protein G:Fc complex involves mainly charged and polar
contacts, whereas protein A and Fc are held together through non-specific
hydrophobic interactions and a few polar interactions. Several residues of Fc
are involved in both the protein G:Fc and the protein A:Fc interaction, which
explains the competitive binding of the two proteins. The apparent differences
in their Fc-binding activities result from additional unique interactions.
|
|
|
|
|
|
|
|
Figure 2.
Figure 2. Schematic representation of the overall fold of
protein G highlighting the eight residues most involved in Fc
binding (Glu27, Lys28, Lys31, Gln32, Asn35, Asp40, Glu42 and
Trp43). β-strands and loop regions are coloured green and
yellow, respectively, and the α-helix is coloured red. Carbon
atoms are coloured yellow, nitrogens are shown in purple and
oxygens in red. Cα-atoms are shown as large cyan spheres.
Figure 2. Schematic representation of the overall fold of
protein G highlighting the eight residues most involved in Fc
binding (Glu27, Lys28, Lys31, Gln32, Asn35, Asp40, Glu42 and
Trp43). β-strands and loop regions are coloured green and
yellow, respectively, and the α-helix is coloured red. Carbon
atoms are coloured yellow, nitrogens are shown in purple and
oxygens in red. Cα-atoms are shown as large cyan spheres.
|
|
Figure 6.
Figure 6. Comparison of the protein G:Fc and protein A:Fc
complexes. Helices and loops in protein A are coloured light and
dark violet, respectively. The colour scheme for protein G and
Fc is as described for Figure 2. (a) Ribbon representation of
the protein G:Fc complex (Cα atoms of Fc residues that interact
with protein G are marked in green). (b) The protein A:Fc
complex (Cα atoms of Fc residues that interact with protein A
are marked in pink). (c) Superposition of the two structures.
The overlay was based on 206 Cα atoms from Fc with an rmsd of
1.16 å. Figure 6. Comparison of the protein G:Fc and
protein A:Fc complexes. Helices and loops in protein A are
coloured light and dark violet, respectively. The colour scheme
for protein G and Fc is as described for [3]Figure 2. (a) Ribbon
representation of the protein G:Fc complex (Cα atoms of Fc
residues that interact with protein G are marked in green). (b)
The protein A:Fc complex (Cα atoms of Fc residues that interact
with protein A are marked in pink). (c) Superposition of the two
structures. The overlay was based on 206 Cα atoms from Fc with
an rmsd of 1.16 å.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Cell Press:
Structure
(1995,
3,
265-278)
copyright 1995.
|
|
|
|
|
|
|
