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Structure of Staphylococcus aureus EsxA suggests a contribution to virulence by action as a transport chaperone and/or adaptor protein.

Sundaramoorthy R, Fyfe PK, Hunter WN
J Mol Biol 383 603-14 (2008)
Cited: 52 times
EuropePMC logo PMID: 18773907

Abstract

Staphylococcus aureus pathogenesis depends on a specialized protein secretion system (ESX-1) that delivers a range of virulence factors to assist infectivity. We report the characterization of two such factors, EsxA and EsxB, small acidic dimeric proteins carrying a distinctive WXG motif. EsxA crystallized in triclinic and monoclinic forms and high-resolution structures were determined. The asymmetric unit of each crystal form is a dimer. The EsxA subunit forms an elongated cylindrical structure created from side-by-side alpha-helices linked with a hairpin bend formed by the WXG motif. Approximately 25% of the solvent accessible surface area of each subunit is involved in interactions, predominantly hydrophobic, with the partner subunit. Secondary-structure predictions suggest that EsxB displays a similar structure. The WXG motif helps to create a shallow cleft at each end of the dimer, forming a short beta-sheet-like feature with an N-terminal segment of the partner subunit. Structural and sequence comparisons, exploiting biological data on related proteins found in Mycobacterium tuberculosis, suggest that this family of proteins may contribute to pathogenesis by transporting protein cargo through the ESX-1 system exploiting a C-terminal secretion signal and/or are capable of acting as adaptor proteins to facilitate interactions with host receptor proteins.

Articles - 2vs0 mentioned but not cited (5)

  1. Structure of Staphylococcus aureus EsxA suggests a contribution to virulence by action as a transport chaperone and/or adaptor protein. Sundaramoorthy R, Fyfe PK, Hunter WN. J. Mol. Biol. 383 603-614 (2008)
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Reviews citing this publication (9)

  1. ESX/type VII secretion systems and their role in host-pathogen interaction. Simeone R, Bottai D, Brosch R. Curr. Opin. Microbiol. 12 4-10 (2009)
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  6. The Enigmatic Esx Proteins: Looking Beyond Mycobacteria. Unnikrishnan M, Constantinidou C, Palmer T, Pallen MJ. Trends Microbiol. 25 192-204 (2017)
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  8. Bacteria-Based Microdevices for the Oral Delivery of Macromolecules. Cao Z, Lin S, Liu J. Pharmaceutics 13 1610 (2021)
  9. Interbacterial competition mediated by the type VIIb secretion system. Boardman ER, Palmer T, Alcock F. Microbiology (Reading) 169 (2023)

Articles citing this publication (38)

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  4. Secretion of atypical protein substrates by the ESAT-6 secretion system of Staphylococcus aureus. Anderson M, Aly KA, Chen YH, Missiakas D. Mol. Microbiol. 90 734-743 (2013)
  5. Staphylococcal Esx proteins modulate apoptosis and release of intracellular Staphylococcus aureus during infection in epithelial cells. Korea CG, Balsamo G, Pezzicoli A, Merakou C, Tavarini S, Bagnoli F, Serruto D, Unnikrishnan M. Infect. Immun. 82 4144-4153 (2014)
  6. Heterogeneity in ess transcriptional organization and variable contribution of the Ess/Type VII protein secretion system to virulence across closely related Staphylocccus aureus strains. Kneuper H, Cao ZP, Twomey KB, Zoltner M, Jäger F, Cargill JS, Chalmers J, van der Kooi-Pol MM, van Dijl JM, Ryan RP, Hunter WN, Palmer T. Mol. Microbiol. 93 928-943 (2014)
  7. Antagonism between Staphylococcus epidermidis and Propionibacterium acnes and its genomic basis. Christensen GJ, Scholz CF, Enghild J, Rohde H, Kilian M, Thürmer A, Brzuszkiewicz E, Lomholt HB, Brüggemann H. BMC Genomics 17 152 (2016)
  8. High levels of DegU-P activate an Esat-6-like secretion system in Bacillus subtilis. Baptista C, Barreto HC, São-José C. PLoS ONE 8 e67840 (2013)
  9. Opposing roles of σB and σB-controlled SpoVG in the global regulation of esxA in Staphylococcus aureus. Schulthess B, Bloes DA, Berger-Bächi B. BMC Microbiol. 12 17 (2012)
  10. Characterization of EssB, a protein required for secretion of ESAT-6 like proteins in Staphylococcus aureus. Chen YH, Anderson M, Hendrickx AP, Missiakas D. BMC Microbiol. 12 219 (2012)
  11. Dimer recognition and secretion by the ESX secretion system in Bacillus subtilis. Sysoeva TA, Zepeda-Rivera MA, Huppert LA, Burton BM. Proc. Natl. Acad. Sci. U.S.A. 111 7653-7658 (2014)
  12. The crystal structure of the Mycobacterium tuberculosis Rv3019c-Rv3020c ESX complex reveals a domain-swapped heterotetramer. Arbing MA, Kaufmann M, Phan T, Chan S, Cascio D, Eisenberg D. Protein Sci. 19 1692-1703 (2010)
  13. The ESX/type VII secretion system modulates development, but not virulence, of the plant pathogen Streptomyces scabies. Fyans JK, Bignell D, Loria R, Toth I, Palmer T. Mol. Plant Pathol. 14 119-130 (2013)
  14. Characterization of Staphylococcus aureus EssB, an integral membrane component of the Type VII secretion system: atomic resolution crystal structure of the cytoplasmic segment. Zoltner M, Fyfe PK, Palmer T, Hunter WN. Biochem. J. 449 469-477 (2013)
  15. Molecular characterization of secretory proteins Rv3619c and Rv3620c from Mycobacterium tuberculosis H37Rv. Mahmood A, Srivastava S, Tripathi S, Ansari MA, Owais M, Arora A. FEBS J. 278 341-353 (2011)
  16. EssD, a Nuclease Effector of the Staphylococcus aureus ESS Pathway. Ohr RJ, Anderson M, Shi M, Schneewind O, Missiakas D. J. Bacteriol. 199 (2017)
  17. EssC: domain structures inform on the elusive translocation channel in the Type VII secretion system. Zoltner M, Ng WM, Money JJ, Fyfe PK, Kneuper H, Palmer T, Hunter WN. Biochem. J. 473 1941-1952 (2016)
  18. Isolation of a Membrane Protein Complex for Type VII Secretion in Staphylococcus aureus. Aly KA, Anderson M, Ohr RJ, Missiakas D. J. Bacteriol. 199 (2017)
  19. Potential of known and short prokaryotic protein motifs as a basis for novel peptide-based antibacterial therapeutics: a computational survey. Ruhanen H, Hurley D, Ghosh A, O'Brien KT, Johnston CR, Shields DC. Front Microbiol 5 4 (2014)
  20. EsxB, a secreted protein from Bacillus anthracis forms two distinct helical bundles. Fan Y, Tan K, Chhor G, Butler EK, Jedrzejczak RP, Missiakas D, Joachimiak A. Protein Sci. 24 1389-1400 (2015)
  21. Crystal structure of hypothetical protein HP0062 (O24902_HELPY) from Helicobacter pylori at 1.65 A resolution. Jang SB, Kwon AR, Son WS, Park SJ, Lee BJ. J. Biochem. 146 535-540 (2009)
  22. Heterogeneity of the group B streptococcal type VII secretion system and influence on colonization of the female genital tract. Spencer BL, Job AM, Robertson CM, Hameed ZA, Serchejian C, Wiafe-Kwakye CS, Mendonça JC, Apolonio MA, Nagao PE, Neely MN, Korotkova N, Korotkov KV, Patras KA, Doran KS. Mol Microbiol 120 258-275 (2023)
  23. Staphylococcus aureus Esx Factors Control Human Dendritic Cell Functions Conditioning Th1/Th17 Response. Cruciani M, Etna MP, Camilli R, Giacomini E, Percario ZA, Severa M, Sandini S, Rizzo F, Brandi V, Balsamo G, Polticelli F, Affabris E, Pantosti A, Bagnoli F, Coccia EM. Front Cell Infect Microbiol 7 330 (2017)
  24. Structural and Functional Dynamics of Staphylococcus aureus Biofilms and Biofilm Matrix Proteins on Different Clinical Materials. Hiltunen AK, Savijoki K, Nyman TA, Miettinen I, Ihalainen P, Peltonen J, Fallarero A. Microorganisms 7 (2019)
  25. RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression. McKellar SW, Ivanova I, Arede P, Zapf RL, Mercier N, Chu LC, Mediati DG, Pickering AC, Briaud P, Foster RG, Kudla G, Fitzgerald JR, Caldelari I, Carroll RK, Tree JJ, Granneman S. Nat Commun 13 3560 (2022)
  26. Metabolite Profiling of Malaysian Gracilaria edulis Reveals Eplerenone as Novel Antibacterial Compound for Drug Repurposing Against MDR Bacteria. Asghar A, Tan YC, Shahid M, Yow YY, Lahiri C. Front Microbiol 12 653562 (2021)
  27. A type VII secretion system of Streptococcus gallolyticus subsp. gallolyticus contributes to gut colonization and the development of colon tumors. Taylor JC, Gao X, Xu J, Holder M, Petrosino J, Kumar R, Liu W, Höök M, Mackenzie C, Hillhouse A, Brashear W, Nunez MP, Xu Y. PLoS Pathog 17 e1009182 (2021)
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  29. Characterization of Foodborne Strains of Staphylococcus aureus by Shotgun Proteomics: Functional Networks, Virulence Factors and Species-Specific Peptide Biomarkers. Carrera M, Böhme K, Gallardo JM, Barros-Velázquez J, Cañas B, Calo-Mata P. Front Microbiol 8 2458 (2017)
  30. Contribution of the EssC ATPase to the assembly of the type 7b secretion system in Staphylococcus aureus. Bobrovskyy M, Oh SY, Missiakas D. J Biol Chem 298 102318 (2022)
  31. Dual Targeting Factors Are Required for LXG Toxin Export by the Bacterial Type VIIb Secretion System. Klein TA, Grebenc DW, Shah PY, McArthur OD, Dickson BH, Surette MG, Kim Y, Whitney JC. mBio 13 e0213722 (2022)
  32. Error-prone PCR mutagenesis and reverse bacterial two-hybrid screening identify a mutation in asparagine 53 of the Staphylococcus aureus ESAT6-like component EsxB that perturbs interaction with EsxD. Ibrahim AM, Ragab YM, Aly KA, Ramadan MA. Folia Microbiol. (Praha) 63 483-492 (2018)
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  34. Leaky barriers to gene sharing between locally co-existing coagulase-negative Staphylococcus species. Ikhimiukor OO, Souza SSR, Marcovici MM, Nye GJ, Gibson R, Andam CP. Commun Biol 6 482 (2023)
  35. Pore-forming Esx proteins mediate toxin secretion by Mycobacterium tuberculosis. Tak U, Dokland T, Niederweis M. Nat Commun 12 394 (2021)
  36. Substrate Interaction with the EssC Coupling Protein of the Type VIIb Secretion System. Mietrach N, Damián-Aparicio D, Mielich-Süss B, Lopez D, Geibel S. J Bacteriol 202 (2020)
  37. The transmembrane domain of the Staphylococcus aureus ESAT-6 component EssB mediates interaction with the integral membrane protein EsaA, facilitating partially regulated secretion in a heterologous host. Ahmed MM, Aboshanab KM, Ragab YM, Missiakas DM, Aly KA. Arch. Microbiol. 200 1075-1086 (2018)
  38. Three small partner proteins facilitate the type VII-dependent secretion of an antibacterial nuclease. Yang Y, Boardman E, Deme J, Alcock F, Lea S, Palmer T. mBio 14 e0210023 (2023)


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