Sortase

Sortase family
Pilus-related Sortase C of Group B Streptococcus. PDB entry 3O0P[1]
Identifiers
Symbol Sortase
Pfam PF04203
InterPro IPR005754
SCOP 1ija
SUPERFAMILY 1ija
OPM superfamily 294
OPM protein 1rz2

Sortase refers to a group of prokaryotic enzymes that modify surface proteins by recognizing and cleaving a carboxyl-terminal sorting signal. For most substrates of sortase enzymes, the recognition signal consists of the motif LPXTG (Leu-Pro-any-Thr-Gly), then a highly hydrophobic transmembrane sequence, followed by a cluster of basic residues such as arginine. Cleavage occurs between the Thr and Gly, with transient attachment through the Thr residue to the active site Cys residue, followed by transpeptidation that attaches the protein covalently to cell wall components. Sortases occur in almost all Gram-positive bacteria and the occasional Gram-negative (e.g. Shewanella putrefaciens) or Archaea (e.g. Methanobacterium thermoautotrophicum), where cell wall LPXTG-mediated decoration has not been reported.[2][3] Although sortase A, the "housekeeping" sortase, typically acts on many protein targets, other forms of sortase recognize variant forms of the cleavage motif, or that catalyze the assembly of pilins into pili.[4][5][6]

Reaction

The Staphylococcus aureus sortase is a transpeptidase that attaches surface proteins to the cell wall; it cleaves between the Gly and Thr of the LPXTG motif and catalyses the formation of an amide bond between the carboxyl-group of threonine and the amino-group of the cell-wall peptidoglycan.[7][8]

Biological role

Substrate proteins attached to cell walls by sortases include enzymes, pilins, and adhesion-mediating large surface glycoproteins. These proteins often play important roles in virulence, infection, and colonization by pathogens.

Surface proteins not only promote interaction between the invading pathogen and animal tissues, but also provide ingenious strategies for bacterial escape from the host's immune response. In the case of S. aureus protein A, immunoglobulins are captured on the microbial surface and camouflage bacteria during the invasion of host tissues. S. aureus mutants lacking the srtA gene fail to anchor and display some surface proteins and are impaired in the ability to cause animal infections. Sortase acts on surface proteins that are initiated into the secretion (Sec) pathway and have their signal peptide removed by signal peptidase. The S. aureus genome encodes two sets of sortase and secretion genes. It is conceivable that S. aureus has evolved more than one pathway for the transport of 20 surface proteins to the cell wall envelope.

Note that exosortase and archaeosortase are functionally analogous, while not in any way homologous to sortase[9].

As an antibiotic target

The sortases are thought to be good targets for new antibiotics[10] as they are important proteins for pathogenic bacteria and some limited commercial interest has been noted by at least one company.[11]

Structure

This group of cysteine peptidases belong to MEROPS peptidase family C60 (clan C-) and include the members of several subfamilies of sortases.

Another sub-family of sortases (C60B in MEROPS) contains bacterial sortase B proteins that are approximately 200 residues long.[12]

Use in structural biology

The transpeptidase activity of sortase is taken advantage of by structural biologists to produce fusion proteins in vitro. The recognition motif (LPXTG) is added to the C-terminus of a protein of interest while an oligo-glycine motif is added to the N-terminus of the second protein to be ligated. Upon addition of sortase to the protein mixture, the two peptides are covalently linked through a native peptide bond. This reaction is employed by NMR spectroscopists to produce NMR invisible solubility tags [13] and in one example by X-ray crystallographers to promote complex formation.[14]

See also

References

  1. ↑ Cozzi, R; Malito, E; Nuccitelli, A; d'Onofrio, M; Martinelli, M; Ferlenghi, I; Grandi, G; Telford, J. L.; Maione, D; Rinaudo, C. D. (2011). "Structure analysis and site-directed mutagenesis of defined key residues and motives for pilus-related sortase C1 in group B Streptococcus". The FASEB Journal. 25 (6): 1874–86. doi:10.1096/fj.10-174797. PMID 21357525.
  2. ↑ Schneewind O, Mazmanian SK, Ton-that H (2001). "Sortase-catalysed anchoring of surface proteins to the cell wall of Staphylococcus aureus". Mol. Microbiol. 40 (5): 1049–1057. doi:10.1046/j.1365-2958.2001.02411.x. PMID 11401711.
  3. ↑ Pallen MJ, Henderson IR, Chaudhuri RR (2003). "Genomic analysis of secretion systems". Curr Opin Microbiol. 6 (5): 519–527. doi:10.1016/j.mib.2003.09.005. PMID 14572546.
  4. ↑ Oh S, Budzik J, Schneewind O (September 2008). "Sortases make pili from three ingredients". Proc Natl Acad Sci U S A. 105 (37): 13703–13704. doi:10.1073/pnas.0807334105. PMC 2544515. PMID 18784365.
  5. ↑ LeMieux J, Woody S, Camilli A (September 2008). "Roles of the sortases of Streptococcus pneumoniae in assembly of the RlrA pilus". J. Bacteriol. 190 (17): 6002–6013. doi:10.1128/JB.00379-08. PMC 2519520. PMID 18606733.
  6. ↑ Kang HJ, Coulibaly F, Proft T, Baker EN (2011). Hofmann A, ed. "Crystal structure of Spy0129, a Streptococcus pyogenes class B sortase involved in pilus assembly". PLoS ONE. 6 (1): e15969. doi:10.1371/journal.pone.0015969. PMC 3019223. PMID 21264317.
  7. ↑ Mazmanian SK, Liu G, Ton-That H, Schneewind O (July 1999). "Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall". Science. 285 (5428): 760–3. doi:10.1126/science.285.5428.760. PMID 10427003.
  8. ↑ Cossart P, Jonquières R (May 2000). "Sortase, a universal target for therapeutic agents against gram-positive bacteria?". Proc. Natl. Acad. Sci. U.S.A. 97 (10): 5013–5. doi:10.1073/pnas.97.10.5013. PMC 33977. PMID 10805759.
  9. ↑ Haft DH, Payne SH, Selengut JD (2012). "Archaeosortases and exosortases are widely distributed systems linking membrane transit with posttranslational modification". J Bacteriol. 194 (1): 36–48. doi:10.1128/JB.06026-11. PMC 3256604. PMID 22037399.
  10. ↑ Maresso AW, Schneewind O (March 2008). "Sortase as a target of anti-infective therapy". Pharmacol. Rev. 60 (1): 128–141. doi:10.1124/pr.107.07110. PMID 18321961.
  11. ↑ SIGA Technologies (September 2006). "Schedule 14A". U.S. Securities and Exchange Commission. Retrieved 29 October 2009.
  12. ↑ Pallen MJ, Lam AC, Antonio M, Dunbar K (March 2001). "An embarrassment of sortases - a richness of substrates?". Trends Microbiol. 9 (3): 97–102. doi:10.1016/S0966-842X(01)01956-4. PMID 11239768.
  13. ↑ Kobashigawa Y, Kumeta H, Ogura K, Inagaki F (January 2009). "Attachment of an NMR-invisible solubility enhancememnt tag using a sortase mediated protein ligation method". Journal of Biomolecular NMR. 43 (3): 145–150. doi:10.1007/s10858-008-9296-5. PMID 19140010.
  14. ↑ Wang Y, Pascoe HG, Brautigam CA, He H, Zhang X (October 2013). "Structural basis for activation and non-canonical catalysis of the Rap GTPase activating protein domain of plexin". eLIFE. 2: e01279. doi:10.7554/eLife.01279. PMC 3787391. PMID 24137545.

Further reading

  • PDB: 3O0P​; Cozzi R, Malito E, Nuccitelli A, D'Onofrio M, Martinelli M, Ferlenghi I, Grandi G, Telford JL, Maione D, Rinaudo CD (February 2011). "Structure analysis and site-directed mutagenesis of defined key residues and motives for pilus-related sortase C1 in group B Streptococcus". FASEB J. 25 (6): 1874–1886. doi:10.1096/fj.10-174797. PMID 21357525.
  • Kang HJ, Paterson NG, Gaspar AH, Ton-That H, Baker EN (October 2009). "The Corynebacterium diphtheriae shaft pilin SpaA is built of tandem Ig-like modules with stabilizing isopeptide and disulfide bonds". Proceedings of the National Academy of Sciences of the United States of America. 106 (40): 16967–16971. doi:10.1073/pnas.0906826106. PMC 2761350. PMID 19805181.
  • Kankainen M, Paulin L, Tynkkynen S, et al. (October 2009). "Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human- mucus binding protein". Proceedings of the National Academy of Sciences of the United States of America. 106 (40): 17193–8. doi:10.1073/pnas.0908876106. PMC 2746127. PMID 19805152.
  • Neiers F, Madhurantakam C, Fälker S, et al. (October 2009). "Two crystal structures of pneumococcal pilus sortase C provide novel insights into catalysis and substrate specificity". Journal of Molecular Biology. 393 (3): 704–16. doi:10.1016/j.jmb.2009.08.058. PMID 19729023.
  • Sillanpää J, Nallapareddy SR, Qin X, et al. (November 2009). "A collagen-binding adhesin, Acb, and ten other putative MSCRAMM and pilus family proteins of Streptococcus gallolyticus subsp. gallolyticus (Streptococcus bovis Group, biotype I)". Journal of Bacteriology. 191 (21): 6643–53. doi:10.1128/JB.00909-09. PMC 2795296. PMID 19717590.
  • Kang HJ, Paterson NG, Baker EN (August 2009). "Expression, purification, crystallization and preliminary crystallographic analysis of SpaA, a major pilin from Corynebacterium diphtheriae". Acta Crystallographica F. 65 (Pt 8): 802–804. doi:10.1107/S1744309109027596. PMC 2720338. PMID 19652344.
  • Guttilla IK, Gaspar AH, Swierczynski A, et al. (September 2009). "Acyl enzyme intermediates in sortase-catalyzed pilus morphogenesis in gram-positive bacteria". Journal of Bacteriology. 191 (18): 5603–12. doi:10.1128/JB.00627-09. PMC 2737948. PMID 19592583.
  • Suree N, Liew CK, Villareal VA, et al. (September 2009). "The structure of the Staphylococcus aureus sortase-substrate complex reveals how the universally conserved LPXTG sorting signal is recognized". The Journal of Biological Chemistry. 284 (36): 24465–77. doi:10.1074/jbc.M109.022624. PMC 2782039. PMID 19592495.
  • Kang HJ, Baker EN (July 2009). "Intramolecular isopeptide bonds give thermodynamic and proteolytic stability to the major pilin protein of Streptococcus pyogenes". The Journal of Biological Chemistry. 284 (31): 20729–20737. doi:10.1074/jbc.M109.014514. PMC 2742838. PMID 19497855.
  • Schlüter S, Franz CM, Gesellchen F, Bertinetti O, Herberg FW, Schmidt FR (August 2009). "The high biofilm-encoding Bee locus: a second pilus gene cluster in Enterococcus faecalis?". Current Microbiology. 59 (2): 206–211. doi:10.1007/s00284-009-9422-y. PMID 19459002.
  • Quigley BR, Zähner D, Hatkoff M, Thanassi DG, Scott JR (June 2009). "Linkage of T3 and Cpa pilins in the Streptococcus pyogenes M3 pilus". Molecular Microbiology. 72 (6): 1379–1394. doi:10.1111/j.1365-2958.2009.06727.x. PMID 19432798.
  • Solovyova AS, Pointon JA, Race PR, Smith WD, Kehoe MA, Banfield MJ (March 2009). "Solution structure of the major (Spy0128) and minor (Spy0125 and Spy0130) pili subunits from Streptococcus pyogenes". European Biophysics Journal. 39 (3): 469–480. doi:10.1007/s00249-009-0432-2. PMID 19290517.
  • Budzik JM, Oh SY, Schneewind O (May 2009). "Sortase D forms the covalent bond that links BcpB to the tip of Bacillus cereus pili". The Journal of Biological Chemistry. 284 (19): 12989–12997. doi:10.1074/jbc.M900927200. PMC 2676031. PMID 19269972.
  • Kang HJ, Middleditch M, Proft T, Baker EN (February 2009). "Isopeptide bonds in bacterial pili and their characterization by X-ray crystallography and mass spectrometry". Biopolymers. 91 (12): 1126–1134. doi:10.1002/bip.21170. PMID 19226623.
  • Manzano C, Contreras-Martel C, El Mortaji L, et al. (December 2008). "Sortase-mediated pilus fiber biogenesis in Streptococcus pneumoniae". Structure. 16 (12): 1838–48. doi:10.1016/j.str.2008.10.007. PMID 19081060.
  • Proft T, Baker EN (February 2009). "Pili in Gram-negative and Gram-positive bacteria - structure, assembly and their role in disease". Cellular and Molecular Life Sciences. 66 (4): 613–635. doi:10.1007/s00018-008-8477-4. PMID 18953686.
  • Budzik JM, Oh SY, Schneewind O (December 2008). "Cell wall anchor structure of BcpA pili in Bacillus anthracis". The Journal of Biological Chemistry. 283 (52): 36676–36686. doi:10.1074/jbc.M806796200. PMC 2605976. PMID 18940793.
  • Mandlik A, Das A, Ton-That H (September 2008). "The molecular switch that activates the cell wall anchoring step of pilus assembly in gram-positive bacteria". Proceedings of the National Academy of Sciences of the United States of America. 105 (37): 14147–14152. doi:10.1073/pnas.0806350105. PMC 2734112. PMID 18779588.
  • Fälker S, Nelson AL, Morfeldt E, et al. (November 2008). "Sortase-mediated assembly and surface topology of adhesive pneumococcal pili". Molecular Microbiology. 70 (3): 595–607. doi:10.1111/j.1365-2958.2008.06396.x. PMC 2680257. PMID 18761697.
  • Budzik JM, Marraffini LA, Souda P, Whitelegge JP, Faull KF, Schneewind O (July 2008). "Amide bonds assemble pili on the surface of bacilli". Proceedings of the National Academy of Sciences of the United States of America. 105 (29): 10215–10220. doi:10.1073/pnas.0803565105. PMC 2481347. PMID 18621716.
  • Nobbs AH, Rosini R, Rinaudo CD, Maione D, Grandi G, Telford JL (August 2008). "Sortase A utilizes an ancillary protein anchor for efficient cell wall anchoring of pili in Streptococcus agalactiae". Infection and Immunity. 76 (8): 3550–3560. doi:10.1128/IAI.01613-07. PMC 2493207. PMID 18541657.
  • Bagnoli F, Moschioni M, Donati C, et al. (August 2008). "A second pilus type in Streptococcus pneumoniae is prevalent in emerging serotypes and mediates adhesion to host cells". Journal of Bacteriology. 190 (15): 5480–92. doi:10.1128/JB.00384-08. PMC 2493256. PMID 18515415.
  • Zähner D, Scott JR (January 2008). "SipA is required for pilus formation in Streptococcus pyogenes serotype M3". Journal of Bacteriology. 190 (2): 527–535. doi:10.1128/JB.01520-07. PMC 2223711. PMID 17993527.
  • Swaminathan A, Mandlik A, Swierczynski A, Gaspar A, Das A, Ton-That H (November 2007). "Housekeeping sortase facilitates the cell wall anchoring of pilus polymers in Corynebacterium diphtheriae". Molecular Microbiology. 66 (4): 961–974. doi:10.1111/j.1365-2958.2007.05968.x. PMC 2841690. PMID 17919283.
  • Budzik JM, Marraffini LA, Schneewind O (October 2007). "Assembly of pili on the surface of Bacillus cereus vegetative cells". Molecular Microbiology. 66 (2): 495–510. doi:10.1111/j.1365-2958.2007.05939.x. PMID 17897374.
  • Kemp KD, Singh KV, Nallapareddy SR, Murray BE (November 2007). "Relative contributions of Enterococcus faecalis OG1RF sortase-encoding genes, srtA and bps (srtC), to biofilm formation and a murine model of urinary tract infection". Infection and Immunity. 75 (11): 5399–5404. doi:10.1128/IAI.00663-07. PMC 2168291. PMID 17785477.
  • Manetti AG, Zingaretti C, Falugi F, et al. (May 2007). "Streptococcus pyogenes pili promote pharyngeal cell adhesion and biofilm formation". Molecular Microbiology. 64 (4): 968–83. doi:10.1111/j.1365-2958.2007.05704.x. PMID 17501921.
  • Mandlik A, Swierczynski A, Das A, Ton-That H (April 2007). "Corynebacterium diphtheriae employs specific minor pilins to target human pharyngeal epithelial cells". Molecular Microbiology. 64 (1): 111–124. doi:10.1111/j.1365-2958.2007.05630.x. PMC 2844904. PMID 17376076.
  • Nallapareddy SR, Singh KV, Sillanpää J, et al. (October 2006). "Endocarditis and biofilm-associated pili of Enterococcus faecalis". The Journal of Clinical Investigation. 116 (10): 2799–807. doi:10.1172/JCI29021. PMC 1578622. PMID 17016560.
  • Scott JR, Zähner D (October 2006). "Pili with strong attachments: Gram-positive bacteria do it differently". Molecular Microbiology. 62 (2): 320–330. doi:10.1111/j.1365-2958.2006.05279.x. PMID 16978260.
  • Swierczynski A, Ton-That H (September 2006). "Type III pilus of corynebacteria: Pilus length is determined by the level of its major pilin subunit". Journal of Bacteriology. 188 (17): 6318–6325. doi:10.1128/JB.00606-06. PMC 1595371. PMID 16923899.
  • Rosini R, Rinaudo CD, Soriani M, et al. (July 2006). "Identification of novel genomic islands coding for antigenic pilus-like structures in Streptococcus agalactiae". Molecular Microbiology. 61 (1): 126–41. doi:10.1111/j.1365-2958.2006.05225.x. PMID 16824100.
  • Dramsi S, Caliot E, Bonne I, et al. (June 2006). "Assembly and role of pili in group B streptococci". Molecular Microbiology. 60 (6): 1401–13. doi:10.1111/j.1365-2958.2006.05190.x. PMID 16796677.
  • Gaspar AH, Ton-That H (February 2006). "Assembly of distinct pilus structures on the surface of Corynebacterium diphtheriae". Journal of Bacteriology. 188 (4): 1526–1533. doi:10.1128/JB.188.4.1526-1533.2006. PMC 1367254. PMID 16452436.
  • Ton-That H, Marraffini LA, Schneewind O (November 2004). "Protein sorting to the cell wall envelope of Gram-positive bacteria". Biochimica et Biophysica Acta. 1694 (1–3): 269–278. doi:10.1016/j.bbamcr.2004.04.014. PMID 15546671.
  • Ton-That H, Marraffini LA, Schneewind O (July 2004). "Sortases and pilin elements involved in pilus assembly of Corynebacterium diphtheriae". Molecular Microbiology. 53 (1): 251–261. doi:10.1111/j.1365-2958.2004.04117.x. PMID 15225319.
  • Ton-That H, Schneewind O (May 2004). "Assembly of pili in Gram-positive bacteria". Trends in Microbiology. 12 (5): 228–234. doi:10.1016/j.tim.2004.03.004. PMID 15120142.
  • Ton-That H, Schneewind O (November 2003). "Assembly of pili on the surface of Corynebacterium diphtheriae". Molecular Microbiology. 50 (4): 1429–1438. doi:10.1046/j.1365-2958.2003.03782.x. PMID 14622427.
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