Bacterial receptor structures

Details Bacterial receptor structures Bacterial receptor structures

1996-08-15

1998-11-03

Caputa, Anthony C.

Chemistry: natural resins or derivatives; peptides or proteins;

Proteins, i.e., more than 100 amino acid residues

530300, 530825, 530402, 5303871, 530386, 530363, 5303884, 530333, 435 691, 435 693, 435 697, 4351721, 435882, 435883, 435 71, 435 6, 436536, 436518, 436501, 436543, 935 10, 935 11, 935 47, C07K 1431, C07K 100, C12P 2100, C12N 100

Patent

active

058310126

DESCRIPTION:

BRIEF SUMMARY
This applications is a 371 of PCT/SE95/00034 filed Jan. 10, 1995 which is a Foreign/PCT application of 9400088-2 filed Jan. 14, 1994.
The present invention relates to a new bacterial receptor structures originating from natural bacterial receptor structures which have been modified in regard to amino acid residues involved in the original interaction function, whereby said original interaction function has been substantially inhibited and replaced by a modified interaction function directed to a desired interaction partner.
Several bacteria known to invade mammals have evolved surface proteins capable of binding to a variety of substances including host specific carbohydrates and proteins. Several such receptors from Gram-positive bacterial pathogens have been isolated and characterized in detail as will be shown below. Most well-characterized are the Fc receptors, named after the capability of binding to the constant Fc part of IgG. Based on binding experiments to IgG from various mammalian sources, and subclasses thereof, Fc receptors have been divided into six types I-VI. The receptor from S. subject of immense studies.
SPA binds IgG from most mammalian species, including man. Of the four subclasses of human IgG, SPA binds to IgG1, and IgG4 but shows very weak 9:4323-4327!. This pseudoimmune reaction has been used for more than 20 years for the purification and detection of antibodies in diagnostic, research and therapeutic applications. Cloning, sequencing and Escherichia coli expression of defined fragments of the SPA gene revealed a M. et al, 1984 J. Biol. Chem. 259:1695-1702; Moks, T. et al, 1986 Eur. J. Biochem. 156:637-643!. A vast number of plasmid vectors have been constructed, allowing gene fusions to different fragments of the gene for and Abrahmsen, L. 1990 Meth. Enz. 185:144-161! (FIG. 2a). of SPA has been determined by X-ray crystallography at a resolution of 2.8 this structure and additional information from NMR experiments, the B domain can be viewed as a compact structure consisting of three anti-parallel .alpha.-helices connected with loops. In the Fc binding, which is of both electrostatic and hydrophobic nature, only side chains of residues from helices 1 and 2 are involved, whilst the third helix is not participating in the binding. Based on this domain B, a synthetic been constructed, suitable as fusion partner for the production of recombinant proteins which allows purification by IgG affinity chromatography. The high solubility and the stable structure of the Z domain has been utilized for production, purification and renaturation of Trends Biotechnol. 6:218-224; Samuelsson, E. et al 1991 Bio. Technol. 9:363-366!.
Streptococcal strains of serological groups C and G display a binding repertoire for mammalian IgGs, including human IgG3, which is even broader than for the type I receptor. The name protein G was suggested for this type III receptor from group G streptococci. In 1986 Olsson and co-workers reported on the cloning and sequencing of the gene from the serological Olsson, A. et al, 1987 Eur. J. Biochem. 168:319-324!. In analogy with SPA is SPG a repetitively arranged molecule, comprising an IgG-binding region 2A). Compared to SPA, SPG displays a different binding spectra for immunoglobulins from different species and subclasses thereof. The IgG binding domains of protein G are now widely used as an immunological tool, i.e. in the affinity purification of monoclonal antibodies. Production of subfragments constructed by DNA-technology, have shown that an individual C-region is sufficient for full IgG-binding. Recently, the structure for a complex between the C1-domain from SPG and human Fc was determined with X-ray crystallography (FIG. 2B). This shows that SPG binds to the CH2-CH3 interface but at a different site compared to SPA. The binding is mainly of electrostatic nature which is in contrast to the large contribution of hydrophobic forces seen for the SPA-Fc interaction. Moreover, the 3-D structure of C1 differs from the X structure in that it is built up by two .beta.-

REFERENCES:
patent: 4879213 (1989-11-01), Fox et al.
patent: 4954618 (1990-09-01), Fahnestock
patent: 5084559 (1992-01-01), Profy
Mutational Analysis of the Interaction Between Staphylococcal Protein A and Human IgG.sub.1, Protein Engineering, Lena Cedergren et al., vol. 6, No. 4, pp. 441-448, 1993.
"Chimeric IgG-Binding Receptors Engineered From Staphylococcal Protein A and Staphylococcal Protein G", The Journal of Biological Chemistry, Margareta Eliasson et al., vol. 263, No. 9, Mar. 25, 1988, pp. 4323-4327.

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