Proteolytic cleavage and cell wall anchoring at the LPXTG motif of surface proteins in gram-positive bacteria.
Many surface proteins are thought to be anchored to the cell wall of Gram-positive bacteria via their C-terminus. Cell wall anchoring requires a specific sorting signal, normally located at the predicted C-terminus of surface proteins. Here we show that when placed into the middle of a polypeptide chain, the sorting signal causes the specific cleavage of the precursor as well as the cell wall anchoring of its N-terminal fragment, while the C-terminal fragment remains within the cytoplasm. N-terminal sequencing of the C-terminal cleavage fragment suggests that the cleavage site is located between threonine (T) and glycine (G) of the LPXTG motif, the signature sequence of cell wall sorting signals. All surface proteins harbouring an LPXTG sequence motif may therefore be cleaved and anchored by a universal mechanism. We also propose a novel hypothesis for the cell wall linkage of surface proteins in Gram-positive bacteria.
Navarre
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Department of Microbiology and Immunology, University of California, Los Angeles, School of Medicine 90024.
Schneewind
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D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002473:Cell Wall / Q000378:metabolism; D017931:DNA Primers; D019286:Endopeptidase K; D010450:Endopeptidases / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D006094:Gram-Positive Bacteria / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008961:Models, Structural; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D010957:Plasmids; D016133:Polymerase Chain Reaction; D012697:Serine Endopeptidases; D013211:Staphylococcus aureus / Q000378:metabolism*
D001426:Bacterial Proteins; D017931:DNA Primers; D008565:Membrane Proteins; D010446:Peptide Fragments; D010450:Endopeptidases; D012697:Serine Endopeptidases; D019286:Endopeptidase K; C026515:type I signal peptidase