title: Membrane cofactor protein (CD46) is a keratinocyte receptor for the M protein of the group A streptococcus.
abstract: The pathogenic Gram-positive bacterium Streptococcus pyogenes (group A streptococcus) is the causative agent of numerous suppurative diseases of human skin. The M protein of S. pyogenes mediates the adherence of the bacterium to keratinocytes, the most numerous cell type in the epidermis. In this study, we have constructed and analyzed a series of mutant M proteins and have shown that the C repeat domain of the M molecule is responsible for cell recognition. The binding of factor H, a serum regulator of complement activation, to the C repeat region of M protein blocked bacterial adherence. Factor H is a member of a large family of complement regulatory proteins that share a homologous structural motif termed the short consensus repeat. Membrane cofactor protein (MCP), or CD46, is a short consensus repeat-containing protein found on the surface of keratinocytes, and purified MCP could competitively inhibit the adherence of S. pyogenes to these cells. Furthermore, the M protein was found to bind directly to MCP, whereas mutant M proteins that lacked the C repeat domain did not bind MCP, suggesting that recognition of MCP plays an important role in the ability of the streptococcus to adhere to keratinocytes.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
authors.forename: N
authors.initials: N
authors.lastname: Okada
authors.forename: M K
authors.initials: MK
authors.lastname: Liszewski
authors.forename: J P
authors.initials: JP
authors.lastname: Atkinson
authors.forename: M
authors.initials: M
authors.lastname: Caparon
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D001667:Binding, Competitive; D002352:Carrier Proteins; D003001:Cloning, Molecular; D016384:Consensus Sequence; D017931:DNA Primers; D006801:Humans; D015603:Keratinocytes / Q000382:microbiology* / Q000502:physiology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D008961:Models, Structural; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D013297:Streptococcus pyogenes / Q000502:physiology*
chemical_list: D000942:Antigens, Bacterial; D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C497857:CD46 protein, human; D002352:Carrier Proteins; D017931:DNA Primers; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C014689:streptococcal M protein