title: A novel variant of the immunoglobulin fold in surface adhesins of Staphylococcus aureus: crystal structure of the fibrinogen-binding MSCRAMM, clumping factor A.
abstract: We report here the crystal structure of the minimal ligand-binding segment of the Staphylococcus aureus MSCRAMM, clumping factor A. This fibrinogen-binding segment contains two similarly folded domains. The fold observed is a new variant of the immunoglobulin motif that we have called DE-variant or the DEv-IgG fold. This subgroup includes the ligand-binding domain of the collagen-binding S.aureus MSCRAMM CNA, and many other structures previously classified as jelly rolls. Structure predictions suggest that the four fibrinogen-binding S.aureus MSCRAMMs identified so far would also contain the same DEv-IgG fold. A systematic docking search using the C-terminal region of the fibrinogen gamma-chain as a probe suggested that a hydrophobic pocket formed between the two DEv-IgG domains of the clumping factor as the ligand-binding site. Mutagenic substitution of residues Tyr256, Pro336, Tyr338 and Lys389 in the clumping factor, which are proposed to contact the terminal residues (408)AGDV(411) of the gamma-chain, resulted in proteins with no or markedly reduced affinity for fibrinogen.
authors.affiliation: Center for Biophysical Sciences and Engineering, School of Optometry, 244 CBSE, 1025 18th Street South, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.
authors.forename: Champion C S
authors.initials: CC
authors.lastname: Deivanayagam
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Wann
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Mike
authors.initials: M
authors.lastname: Carson
authors.forename: Kanagalaghatta R
authors.initials: KR
authors.lastname: Rajashankar
authors.forename: Magnus
authors.initials: M
authors.lastname: Höök
authors.forename: Sthanam V L
authors.initials: SV
authors.lastname: Narayana
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry*; D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D011392:Proline / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry
chemical_list: D018829:Adhesins, Bacterial; D007136:Immunoglobulins; D011994:Recombinant Proteins; D014443:Tyrosine; D005340:Fibrinogen; D011392:Proline; D008239:Lysine