Molecular characterization of the S-layer gene, sbpA, of Bacillus sphaericus CCM 2177 and production of a functional S-layer fusion protein with the ability to recrystallize in a defined orientation while presenting the fused allergen

Appl Environ Microbiol. 2002 Jul;68(7):3251-60. doi: 10.1128/AEM.68.7.3251-3260.2002.

Abstract

The nucleotide sequence encoding the crystalline bacterial cell surface (S-layer) protein SbpA of Bacillus sphaericus CCM 2177 was determined by a PCR-based technique using four overlapping fragments. The entire sbpA sequence indicated one open reading frame of 3,804 bp encoding a protein of 1,268 amino acids with a theoretical molecular mass of 132,062 Da and a calculated isoelectric point of 4.69. The N-terminal part of SbpA, which is involved in anchoring the S-layer subunits via a distinct type of secondary cell wall polymer to the rigid cell wall layer, comprises three S-layer-homologous motifs. For screening of amino acid positions located on the outer surface of the square S-layer lattice, the sequence encoding Strep-tag I, showing affinity to streptavidin, was linked to the 5' end of the sequence encoding the recombinant S-layer protein (rSbpA) or a C-terminally truncated form (rSbpA(31-1068)). The deletion of 200 C-terminal amino acids did not interfere with the self-assembly properties of the S-layer protein but significantly increased the accessibility of Strep-tag I. Thus, the sequence encoding the major birch pollen allergen (Bet v1) was fused via a short linker to the sequence encoding the C-terminally truncated form rSpbA(31-1068). Labeling of the square S-layer lattice formed by recrystallization of rSbpA(31-1068)/Bet v1 on peptidoglycan-containing sacculi with a Bet v1-specific monoclonal mouse antibody demonstrated the functionality of the fused protein sequence and its location on the outer surface of the S-layer lattice. The specific interactions between the N-terminal part of SbpA and the secondary cell wall polymer will be exploited for an oriented binding of the S-layer fusion protein on solid supports to generate regularly structured functional protein lattices.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus / genetics*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics*
  • Cloning, Molecular
  • Copper / chemistry
  • Crystallization
  • Escherichia coli
  • Gene Expression
  • Immunohistochemistry
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics*
  • Monosaccharide Transport Proteins / genetics*
  • Monosaccharide Transport Proteins / isolation & purification
  • Peptide Fragments / genetics
  • Polylysine / chemistry
  • Recombinant Fusion Proteins / chemistry

Substances

  • Bacterial Proteins
  • Membrane Glycoproteins
  • Monosaccharide Transport Proteins
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • S-layer proteins
  • SbpA protein, bacteria
  • Polylysine
  • Copper