title: Decorin-binding sites in the adhesin DbpA from Borrelia burgdorferi: a synthetic peptide approach.
abstract: Lyme disease is caused by the spirochete Borrelia burgdorferi following transmission from infected Ixodes ticks to human hosts. Following colonization of the skin, spirochetes can disseminate throughout the body, resulting in complications that can include ocular, cardiac, neural, and skeletal disease. We have previously shown that B. burgdorferi expresses two closely related decorin-binding adhesins (DbpA and DbpB) of the MSCRAMM (microbial surface component recognizing adhesive matrix molecule) type that can mediate bacterial attachment to extracellular matrices in the host. Furthermore, three Lys residues in DbpA appear to be critical for the binding of DbpA to decorin. We have now characterized the interaction of DbpA and decorin further by using a synthetic peptide approach. We synthesized a panel of peptides that spanned the DbpA sequence and examined their ability to inhibit the binding of intact DbpA to decorin. From these studies, we identified a decorin-binding peptide that lost this activity if the sequence was either scrambled or if a critical Lys residue was chemically modified. A minimal decorin-binding peptide was identified by examining a set of truncated peptides. One peptide is proposed to contain the primary decorin-binding site in DbpA. By comparing the amino acid sequences of 29 different DbpA homologs from different B. burgdorferi sensu lato isolates, we discovered that the identified decorin-binding sequence was quite variable. Therefore, we synthesized a new panel of peptides containing the putative decorin-binding sequence of the different DbpA homologs. All of these peptides were active in our decorin-binding assay, and consensus decorin binding motifs are discussed.
authors.affiliation: Center for Extracellular Matrix Biology, Albert B. Alkek Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas 77030, USA.
authors.forename: Dagmar Sandbäck
authors.initials: DS
authors.lastname: Pikas
authors.forename: Eric L
authors.initials: EL
authors.lastname: Brown
authors.forename: Sivashankarappa
authors.initials: S
authors.lastname: Gurusiddappa
authors.forename: Lawrence Y
authors.initials: LY
authors.lastname: Lee
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Magnus
authors.initials: M
authors.lastname: Höök
mesh_terms: D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D025065:Borrelia burgdorferi / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D058575:Decorin; D016326:Extracellular Matrix Proteins; D008239:Lysine; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D000906:Antibodies; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; C546878:DCN protein, human; C546879:Dcn protein, mouse; C112557:DdpB protein, Borrelia burgdorferi; D058575:Decorin; D016326:Extracellular Matrix Proteins; D010455:Peptides; D011509:Proteoglycans; D008239:Lysine