CRYSTAL STRUCTURE OF THE C2 FRAGMENT OF STREPTOCOCCAL PROTEIN-G IN COMPLEX WITH THE FC DOMAIN OF HUMAN-IGG
1995 (English)In: STRUCTURE, ISSN 0969-2126, Vol. 3, no 3, 265-278 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
1995. Vol. 3, no 3, 265-278 p.
IMMUNOGLOBULIN; MOLECULAR RECOGNITION; PROTEIN G; PROTEIN-PROTEIN COMPLEX; X-RAY CRYSTALLOGRAPHY; IMMUNOGLOBULIN-BINDING DOMAIN; HIV-1 REVERSE-TRANSCRIPTASE; STAPHYLOCOCCUS-AUREUS; CRYSTALLOGRAPHIC REFINEMENT; RIBONUCLEASE-H; B-DOMAIN; RESOLUTION; REGIONS
IdentifiersURN: urn:nbn:se:uu:diva-80526OAI: oai:DiVA.org:uu-80526DiVA: diva2:108440