• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of embojLink to Publisher's site
EMBO J. Dec 1993; 12(12): 4803–4811.
PMCID: PMC413927

Cell wall sorting signals in surface proteins of gram-positive bacteria.

Abstract

Staphylococcal protein A is anchored to the cell wall, a unique cellular compartment of Gram-positive bacteria. The sorting signal sufficient for cell wall anchoring consists of an LPXTG motif, a C-terminal hydrophobic domain and a charged tail. Homologous sequences are found in many surface proteins of Gram-positive bacteria and we explored the universality of these sequences to serve as cell wall sorting signals. We show that several signals are able to anchor fusion proteins to the staphylococcal cell wall. Some signals do not sort effectively, but acquire sorting activity once the spacing between the LPXTG motif and the charged tail has been increased to span the same length as in protein A. Thus, signals for cell wall anchoring in Gram-positive bacteria are as universal as signal (leader) sequences.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Baranski TJ, Faust PL, Kornfeld S. Generation of a lysosomal enzyme targeting signal in the secretory protein pepsinogen. Cell. 1990 Oct 19;63(2):281–291. [PubMed]
  • Blobel G. Intracellular protein topogenesis. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1496–1500. [PMC free article] [PubMed]
  • Brown DA, Rose JK. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell. 1992 Feb 7;68(3):533–544. [PubMed]
  • BRUMFITT W, WARDLAW AC, PARK JT. Development of lysozyme-resistance in Micrococcus lysodiekticus and its association with an increased O-acetyl content of the cell wall. Nature. 1958 Jun 28;181(4626):1783–1784. [PubMed]
  • Chang S, Cohen SN. High frequency transformation of Bacillus subtilis protoplasts by plasmid DNA. Mol Gen Genet. 1979 Jan 5;168(1):111–115. [PubMed]
  • Collawn JF, Stangel M, Kuhn LA, Esekogwu V, Jing SQ, Trowbridge IS, Tainer JA. Transferrin receptor internalization sequence YXRF implicates a tight turn as the structural recognition motif for endocytosis. Cell. 1990 Nov 30;63(5):1061–1072. [PubMed]
  • Cosson P, Bonifacino JS. Role of transmembrane domain interactions in the assembly of class II MHC molecules. Science. 1992 Oct 23;258(5082):659–662. [PubMed]
  • Cosson P, Lankford SP, Bonifacino JS, Klausner RD. Membrane protein association by potential intramembrane charge pairs. Nature. 1991 May 30;351(6325):414–416. [PubMed]
  • Davis NG, Model P. An artificial anchor domain: hydrophobicity suffices to stop transfer. Cell. 1985 Jun;41(2):607–614. [PubMed]
  • Davis NG, Boeke JD, Model P. Fine structure of a membrane anchor domain. J Mol Biol. 1985 Jan 5;181(1):111–121. [PubMed]
  • Ferretti JJ, Russell RR, Dao ML. Sequence analysis of the wall-associated protein precursor of Streptococcus mutans antigen A. Mol Microbiol. 1989 Apr;3(4):469–478. [PubMed]
  • Gaillard JL, Berche P, Frehel C, Gouin E, Cossart P. Entry of L. monocytogenes into cells is mediated by internalin, a repeat protein reminiscent of surface antigens from gram-positive cocci. Cell. 1991 Jun 28;65(7):1127–1141. [PubMed]
  • GAREN A, ZINDER ND. Radiological evidence for partial genetic homology between bacteriophage and host bacteria. Virology. 1955 Nov;1(4):347–376. [PubMed]
  • Gennity JM, Inouye M. The protein sequence responsible for lipoprotein membrane localization in Escherichia coli exhibits remarkable specificity. J Biol Chem. 1991 Sep 5;266(25):16458–16464. [PubMed]
  • Ghuysen JM. Use of bacteriolytic enzymes in determination of wall structure and their role in cell metabolism. Bacteriol Rev. 1968 Dec;32(4 Pt 2):425–464. [PMC free article] [PubMed]
  • GHUYSEN JM, STROMINGER JL. STRUCTURE OF THE CELL WALL OF STAPHYLOCOCCUS AUREUS, STRAIN COPENHAGEN. II. SEPARATION AND STRUCTURE OF DISACCHARIDES. Biochemistry. 1963 Sep-Oct;2:1119–1125. [PubMed]
  • Goldschmidt RM, Thoren-Gordon M, Curtiss R., 3rd Regions of the Streptococcus sobrinus spaA gene encoding major determinants of antigen I. J Bacteriol. 1990 Jul;172(7):3988–4001. [PMC free article] [PubMed]
  • Gottschalk S, Waheed A, Schmidt B, Laidler P, von Figura K. Sequential processing of lysosomal acid phosphatase by a cytoplasmic thiol proteinase and a lysosomal aspartyl proteinase. EMBO J. 1989 Nov;8(11):3215–3219. [PMC free article] [PubMed]
  • Guss B, Uhlén M, Nilsson B, Lindberg M, Sjöquist J, Sjödahl J. Region X, the cell-wall-attachment part of staphylococcal protein A. Eur J Biochem. 1984 Jan 16;138(2):413–420. [PubMed]
  • Gutierrez L, Magee AI, Marshall CJ, Hancock JF. Post-translational processing of p21ras is two-step and involves carboxyl-methylation and carboxy-terminal proteolysis. EMBO J. 1989 Apr;8(4):1093–1098. [PMC free article] [PubMed]
  • Hash JH, Rothlauf MV. The N,O-diacetylmuramidase of Chalaropsis species. I. Purification and crystallization. J Biol Chem. 1967 Dec 10;242(23):5586–5590. [PubMed]
  • HASH JH, WISHNICK M, MILLER PA. FORMATION OF "PROTOPLASTS" OF STAPHYLOCOCCUS AUREUS WITH A FUNGAL N-ACETYLHEXOSAMINIDASE. J Bacteriol. 1964 Feb;87:432–437. [PMC free article] [PubMed]
  • Hedén LO, Frithz E, Lindahl G. Molecular characterization of an IgA receptor from group B streptococci: sequence of the gene, identification of a proline-rich region with unique structure and isolation of N-terminal fragments with IgA-binding capacity. Eur J Immunol. 1991 Jun;21(6):1481–1490. [PubMed]
  • Hollingshead SK, Fischetti VA, Scott JR. Complete nucleotide sequence of type 6 M protein of the group A Streptococcus. Repetitive structure and membrane anchor. J Biol Chem. 1986 Feb 5;261(4):1677–1686. [PubMed]
  • Jackson MR, Nilsson T, Peterson PA. Retrieval of transmembrane proteins to the endoplasmic reticulum. J Cell Biol. 1993 Apr;121(2):317–333. [PMC free article] [PubMed]
  • Jones CL, Khan SA. Nucleotide sequence of the enterotoxin B gene from Staphylococcus aureus. J Bacteriol. 1986 Apr;166(1):29–33. [PMC free article] [PubMed]
  • Kao SM, Olmsted SB, Viksnins AS, Gallo JC, Dunny GM. Molecular and genetic analysis of a region of plasmid pCF10 containing positive control genes and structural genes encoding surface proteins involved in pheromone-inducible conjugation in Enterococcus faecalis. J Bacteriol. 1991 Dec;173(23):7650–7664. [PMC free article] [PubMed]
  • Kocks C, Gouin E, Tabouret M, Berche P, Ohayon H, Cossart P. L. monocytogenes-induced actin assembly requires the actA gene product, a surface protein. Cell. 1992 Feb 7;68(3):521–531. [PubMed]
  • Kreiswirth BN, Löfdahl S, Betley MJ, O'Reilly M, Schlievert PM, Bergdoll MS, Novick RP. The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage. Nature. 1983 Oct 20;305(5936):709–712. [PubMed]
  • Lemmon MA, Flanagan JM, Treutlein HR, Zhang J, Engelman DM. Sequence specificity in the dimerization of transmembrane alpha-helices. Biochemistry. 1992 Dec 29;31(51):12719–12725. [PubMed]
  • Lobel P, Fujimoto K, Ye RD, Griffiths G, Kornfeld S. Mutations in the cytoplasmic domain of the 275 kd mannose 6-phosphate receptor differentially alter lysosomal enzyme sorting and endocytosis. Cell. 1989 Jun 2;57(5):787–796. [PubMed]
  • Nilsson B, Abrahmsén L, Uhlén M. Immobilization and purification of enzymes with staphylococcal protein A gene fusion vectors. EMBO J. 1985 Apr;4(4):1075–1080. [PMC free article] [PubMed]
  • Novick R. Properties of a cryptic high-frequency transducing phage in Staphylococcus aureus. Virology. 1967 Sep;33(1):155–166. [PubMed]
  • Pancholi V, Fischetti VA. Isolation and characterization of the cell-associated region of group A streptococcal M6 protein. J Bacteriol. 1988 Jun;170(6):2618–2624. [PMC free article] [PubMed]
  • Patti JM, Jonsson H, Guss B, Switalski LM, Wiberg K, Lindberg M, Hök M. Molecular characterization and expression of a gene encoding a Staphylococcus aureus collagen adhesin. J Biol Chem. 1992 Mar 5;267(7):4766–4772. [PubMed]
  • Pelham HR, Hardwick KG, Lewis MJ. Sorting of soluble ER proteins in yeast. EMBO J. 1988 Jun;7(6):1757–1762. [PMC free article] [PubMed]
  • Pryer NK, Wuestehube LJ, Schekman R. Vesicle-mediated protein sorting. Annu Rev Biochem. 1992;61:471–516. [PubMed]
  • Ranelli DM, Jones CL, Johns MB, Mussey GJ, Khan SA. Molecular cloning of staphylococcal enterotoxin B gene in Escherichia coli and Staphylococcus aureus. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5850–5854. [PMC free article] [PubMed]
  • SCHINDLER CA, SCHUHARDT VT. LYSOSTAPHIN: A NEW BACTERIOLYTIC AGENT FOR THE STAPHYLOCOCCUS. Proc Natl Acad Sci U S A. 1964 Mar;51:414–421. [PMC free article] [PubMed]
  • Schneewind O, Jones KF, Fischetti VA. Sequence and structural characteristics of the trypsin-resistant T6 surface protein of group A streptococci. J Bacteriol. 1990 Jun;172(6):3310–3317. [PMC free article] [PubMed]
  • Schneewind O, Model P, Fischetti VA. Sorting of protein A to the staphylococcal cell wall. Cell. 1992 Jul 24;70(2):267–281. [PubMed]
  • Signäs C, Raucci G, Jönsson K, Lindgren PE, Anantharamaiah GM, Hök M, Lindberg M. Nucleotide sequence of the gene for a fibronectin-binding protein from Staphylococcus aureus: use of this peptide sequence in the synthesis of biologically active peptides. Proc Natl Acad Sci U S A. 1989 Jan;86(2):699–703. [PMC free article] [PubMed]
  • Sjöquist J, Meloun B, Hjelm H. Protein A isolated from Staphylococcus aureus after digestion with lysostaphin. Eur J Biochem. 1972 Sep 25;29(3):572–578. [PubMed]
  • Sjöquist J, Movitz J, Johansson IB, Hjelm H. Localization of protein A in the bacteria. Eur J Biochem. 1972 Oct 17;30(1):190–194. [PubMed]
  • Strominger JL, Ghuysen JM. Mechanisms of enzymatic bacteriaolysis. Cell walls of bacteri are solubilized by action of either specific carbohydrases or specific peptidases. Science. 1967 Apr 14;156(3772):213–221. [PubMed]
  • Switalski LM, Patti JM, Butcher W, Gristina AG, Speziale P, Hök M. A collagen receptor on Staphylococcus aureus strains isolated from patients with septic arthritis mediates adhesion to cartilage. Mol Microbiol. 1993 Jan;7(1):99–107. [PubMed]
  • Tipper DJ, Strominger JL, Ensign JC. Structure of the cell wall of Staphylococcus aureus, strain Copenhagen. VII. Mode of action of the bacteriolytic peptidase from Myxobacter and the isolation of intact cell wall polysaccharides. Biochemistry. 1967 Mar;6(3):906–920. [PubMed]
  • Tokuda M, Okahashi N, Takahashi I, Nakai M, Nagaoka S, Kawagoe M, Koga T. Complete nucleotide sequence of the gene for a surface protein antigen of Streptococcus sobrinus. Infect Immun. 1991 Sep;59(9):3309–3312. [PMC free article] [PubMed]
  • Tweten RK, Iandolo JJ. Transport and processing of staphylococcal enterotoxin B. J Bacteriol. 1983 Jan;153(1):297–303. [PMC free article] [PubMed]
  • Uhlén M, Guss B, Nilsson B, Gatenbeck S, Philipson L, Lindberg M. Complete sequence of the staphylococcal gene encoding protein A. A gene evolved through multiple duplications. J Biol Chem. 1984 Feb 10;259(3):1695–1702. [PubMed]
  • Yeung MK, Cisar JO. Sequence homology between the subunits of two immunologically and functionally distinct types of fimbriae of Actinomyces spp. J Bacteriol. 1990 May;172(5):2462–2468. [PMC free article] [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...