X-ray structure of Na-ASP-2, a pathogenesis-related-1 protein from the nematode parasite, Necator americanus, and a vaccine antigen for human hookworm infection

Oluwatoyin A. Asojo, Gaddam Goud, Kajari Dhar, Alex Loukas, Bin Zhan, Vehid Deumic, Sen Liu, Gloria E Borgstahl, Peter J. Hotez

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Human hookworm infection is a major cause of anemia and malnutrition of adults and children in the developing world. As part of on-going efforts to control hookworm infection, The Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective L3 larval stages of the parasite, including a family of pathogenesis-related (PR) proteins known as the Ancylostoma-secreted proteins (ASPs). A novel crystal structure of Na-ASP-2, a PR-1 protein secreted by infective larvae of the human hookworm Necator americanus, has been solved to resolution limits of 1.68 Å and to an R-factor of 17% using the recombinant protein expressed in and secreted by Pichia pastoris. The overall fold of Na-ASP-2 is a three-layer αβα sandwich flanked by an N-terminal loop and a short, cysteine-rich C terminus. Our structure reveals a large central cavity that is flanked by His129 and Glu106, two residues that are well conserved in all parasitic nematode L3 ASPs. Na-ASP-2 has structural and charge similarities to chemokines, which suggests that Na-ASP-2 may be an extra-cellular ligand of an unknown receptor. Na-ASP-2 is a useful homology model for NIF, a natural antagonistic ligand of CR3 receptor. From these modeling studies, possible binding modes were predicted. In addition, this first structure of a PR-1 protein from parasitic helminths may shed light on the molecular basis of host-parasite interactions.

Original languageEnglish (US)
Pages (from-to)801-814
Number of pages14
JournalJournal of Molecular Biology
Volume346
Issue number3
DOIs
StatePublished - Feb 25 2005

Fingerprint

Necator americanus
Hookworm Infections
Ancylostoma
Parasites
Vaccines
X-Rays
Antigens
Proteins
Ancylostomatoidea
Helminth Proteins
R388
Macrophage-1 Antigen
Child Nutrition Disorders
Ligands
Host-Parasite Interactions
Pichia
Chemokines
Recombinant Proteins
Cysteine
Larva

Keywords

  • ASP
  • Crystal structure
  • Hookworm
  • Necator americanus
  • Pathogenesis-related protein

ASJC Scopus subject areas

  • Molecular Biology

Cite this

X-ray structure of Na-ASP-2, a pathogenesis-related-1 protein from the nematode parasite, Necator americanus, and a vaccine antigen for human hookworm infection. / Asojo, Oluwatoyin A.; Goud, Gaddam; Dhar, Kajari; Loukas, Alex; Zhan, Bin; Deumic, Vehid; Liu, Sen; Borgstahl, Gloria E; Hotez, Peter J.

In: Journal of Molecular Biology, Vol. 346, No. 3, 25.02.2005, p. 801-814.

Research output: Contribution to journalArticle

Asojo, Oluwatoyin A. ; Goud, Gaddam ; Dhar, Kajari ; Loukas, Alex ; Zhan, Bin ; Deumic, Vehid ; Liu, Sen ; Borgstahl, Gloria E ; Hotez, Peter J. / X-ray structure of Na-ASP-2, a pathogenesis-related-1 protein from the nematode parasite, Necator americanus, and a vaccine antigen for human hookworm infection. In: Journal of Molecular Biology. 2005 ; Vol. 346, No. 3. pp. 801-814.
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