PDBsum entry 1fcc

Complex (antibody/antigen)

PDB id: 1fcc

Contents

Protein chains

206 a.a. *

56 a.a. *

* Residue conservation analysis

PDB id:

1fcc

Name:

Complex (antibody/antigen)

Title:

Crystal structure of the c2 fragment of streptococcal protein g in complex with the fc domain of human igg

Structure:

Igg1 mo61 fc. Chain: a, b. Engineered: yes. Streptococcal protein g (c2 fragment). Chain: c, d. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: hybridoma. Gene: n-terminal fragment of. Expressed in: escherichia coli. Expression_system_taxid: 562. Streptococcus. Organism_taxid: 1301.

Biol. unit:

Octamer (from PQS)

Resolution:

3.20Å R-factor: 0.289 R-free: 0.357

Authors:

A.E.Sauer-Eriksson,G.J.Kleywegt,M.Uhlen,T.A.Jones

Key ref:

A.E.Sauer-Eriksson et al. (1995). Crystal structure of the C2 fragment of streptococcal protein G in complex with the Fc domain of human IgG. Structure, 3, 265-278. PubMed id: 7788293 DOI: 10.1016/S0969-2126(01)00157-5

Date:

17-Jan-95 Release date: 20-Apr-95

Protein chains

P01857  (IGHG1_HUMAN) -  Immunoglobulin heavy constant gamma 1 from Homo sapiens

Seq: 399 a.a.

Struc: 206 a.a.*

Protein chains

P19909  (SPG2_STRSG) -  Immunoglobulin G-binding protein G from Streptococcus sp. group G

Seq: 593 a.a.

Struc: 56 a.a.

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

DOI no: 10.1016/S0969-2126(01)00157-5

Structure 3:265-278 (1995)

PubMed id: 7788293

Crystal structure of the C2 fragment of streptococcal protein G in complex with the Fc domain of human IgG.

A.E.Sauer-Eriksson, G.J.Kleywegt, M.Uhlén, T.A.Jones.

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.

Selected figure(s)

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.

Figures were selected by an automated process.