Ghent University Academic Bibliography

Advanced

Structure of Ostertagia ostertagi ASP-1: insights into disulfide-mediated cyclization and dimerization

Jimmy Borloo UGent, Peter Geldhof UGent, Iris Peelaers UGent, Frederik Van Meulder UGent, Paul Ameloot, Nico Callewaert UGent, Jozef Vercruysse UGent, Edwin Claerebout UGent, Sergei V Strelkov and Stephen D Weeks (2013) ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY. 69(4). p.493-503
abstract
The cysteine-rich secretory/antigen 5/pathogenesis-related 1 (CAP) protein superfamily is composed of a functionally diverse group of members that are found in both eukaryotes and prokaryotes. The excretome/secretome of numerous helminths (parasitic nematodes) contains abundant amounts of CAP members termed activation-associated secreted proteins (ASPs). Although ASPs are necessary for the parasitic life cycle in the host, the current lack of structural and functional information limits both understanding of their actual role in hostparasite interactions and the development of new routes in controlling parasitic infections and diseases. Alleviating this knowledge gap, a 1.85 angstrom resolution structure of recombinantly produced Oo-ASP-1 from Ostertagia ostertagi, which is one of the most prevalent gastrointestinal parasites in cattle worldwide, was solved. Overall, Oo-ASP-1 displays the common hallmark architecture shared by all CAP-superfamily members, including the N-terminal CAP and C-terminal cysteine-rich domains, but it also reveals a number of highly peculiar features. In agreement with studies of the natively produced protein, the crystal structure shows that Oo-ASP-1 forms a stable dimer that has been found to be primarily maintained via an intermolecular disulfide bridge, hence the small interaction surface of only 306.8 angstrom 2. Moreover, unlike any other ASP described to date, an additional intramolecular disulfide bridge links the N- and C-termini of each monomer, thereby yielding a quasi-cyclic molecule. Taken together, the insights presented here form an initial step towards a better understanding of the actual biological role(s) that this ASP plays in hostparasite interactions. The structure is also essential to help to define the key regions of the protein suitable for development of ASP-based vaccines, which would enable the current issues surrounding anthelmintic resistance in the treatment of parasitic infections and diseases to be circumvented.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
activation-associated secreted proteins, CAP-superfamily proteins, Ostertagia ostertagi, disulfide-bridge-mediated cyclization and dimerization, ASP classification, PATHOGENESIS-RELATED PROTEIN, MULTIPLE SEQUENCE ALIGNMENT, RICH SECRETORY PROTEIN, ANCYLOSTOMA-CANINUM, CRYSTAL-STRUCTURE, MOLECULAR-REPLACEMENT, NECATOR-AMERICANUS, HIGH-THROUGHPUT, HOOKWORM, SUPERFAMILY
journal title
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
Acta Crystallogr. Sect. D-Biol. Crystallogr.
volume
69
issue
4
pages
493 - 503
Web of Science type
Article
Web of Science id
000316743300001
JCR category
CRYSTALLOGRAPHY
JCR impact factor
7.232 (2013)
JCR rank
1/23 (2013)
JCR quartile
1 (2013)
ISSN
0907-4449
DOI
10.1107/S0907444912050019
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
3196461
handle
http://hdl.handle.net/1854/LU-3196461
date created
2013-04-18 15:15:36
date last changed
2016-12-19 15:46:52
@article{3196461,
  abstract     = {The cysteine-rich secretory/antigen 5/pathogenesis-related 1 (CAP) protein superfamily is composed of a functionally diverse group of members that are found in both eukaryotes and prokaryotes. The excretome/secretome of numerous helminths (parasitic nematodes) contains abundant amounts of CAP members termed activation-associated secreted proteins (ASPs). Although ASPs are necessary for the parasitic life cycle in the host, the current lack of structural and functional information limits both understanding of their actual role in hostparasite interactions and the development of new routes in controlling parasitic infections and diseases. Alleviating this knowledge gap, a 1.85 angstrom resolution structure of recombinantly produced Oo-ASP-1 from Ostertagia ostertagi, which is one of the most prevalent gastrointestinal parasites in cattle worldwide, was solved. Overall, Oo-ASP-1 displays the common hallmark architecture shared by all CAP-superfamily members, including the N-terminal CAP and C-terminal cysteine-rich domains, but it also reveals a number of highly peculiar features. In agreement with studies of the natively produced protein, the crystal structure shows that Oo-ASP-1 forms a stable dimer that has been found to be primarily maintained via an intermolecular disulfide bridge, hence the small interaction surface of only 306.8 angstrom 2. Moreover, unlike any other ASP described to date, an additional intramolecular disulfide bridge links the N- and C-termini of each monomer, thereby yielding a quasi-cyclic molecule. Taken together, the insights presented here form an initial step towards a better understanding of the actual biological role(s) that this ASP plays in hostparasite interactions. The structure is also essential to help to define the key regions of the protein suitable for development of ASP-based vaccines, which would enable the current issues surrounding anthelmintic resistance in the treatment of parasitic infections and diseases to be circumvented.},
  author       = {Borloo, Jimmy and Geldhof, Peter and Peelaers, Iris and Van Meulder, Frederik and Ameloot, Paul and Callewaert, Nico and Vercruysse, Jozef and Claerebout, Edwin and Strelkov, Sergei V and Weeks, Stephen D},
  issn         = {0907-4449},
  journal      = {ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY},
  keyword      = {activation-associated secreted proteins,CAP-superfamily proteins,Ostertagia ostertagi,disulfide-bridge-mediated cyclization and dimerization,ASP classification,PATHOGENESIS-RELATED PROTEIN,MULTIPLE SEQUENCE ALIGNMENT,RICH SECRETORY PROTEIN,ANCYLOSTOMA-CANINUM,CRYSTAL-STRUCTURE,MOLECULAR-REPLACEMENT,NECATOR-AMERICANUS,HIGH-THROUGHPUT,HOOKWORM,SUPERFAMILY},
  language     = {eng},
  number       = {4},
  pages        = {493--503},
  title        = {Structure of Ostertagia ostertagi ASP-1: insights into disulfide-mediated cyclization and dimerization},
  url          = {http://dx.doi.org/10.1107/S0907444912050019},
  volume       = {69},
  year         = {2013},
}

Chicago
Borloo, Jimmy, Peter Geldhof, Iris Peelaers, Frederik Van Meulder, Paul Ameloot, Nico Callewaert, Jozef Vercruysse, Edwin Claerebout, Sergei V Strelkov, and Stephen D Weeks. 2013. “Structure of Ostertagia Ostertagi ASP-1: Insights into Disulfide-mediated Cyclization and Dimerization.” Acta Crystallographica Section D-biological Crystallography 69 (4): 493–503.
APA
Borloo, J., Geldhof, P., Peelaers, I., Van Meulder, F., Ameloot, P., Callewaert, N., Vercruysse, J., et al. (2013). Structure of Ostertagia ostertagi ASP-1: insights into disulfide-mediated cyclization and dimerization. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 69(4), 493–503.
Vancouver
1.
Borloo J, Geldhof P, Peelaers I, Van Meulder F, Ameloot P, Callewaert N, et al. Structure of Ostertagia ostertagi ASP-1: insights into disulfide-mediated cyclization and dimerization. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY. 2013;69(4):493–503.
MLA
Borloo, Jimmy, Peter Geldhof, Iris Peelaers, et al. “Structure of Ostertagia Ostertagi ASP-1: Insights into Disulfide-mediated Cyclization and Dimerization.” ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY 69.4 (2013): 493–503. Print.