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.

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 A 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 alphabetaalpha 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.

• Authors: Oluwatoyin A Asojo, Gaddam Goud, Kajari Dhar, Alex Loukas, Bin Zhan, Vehid Deumic, Sen Liu, Gloria E O Borgstahl, Peter J Hotez
• Journal: Journal of molecular biology (J Mol Biol) Vol. 346 Issue 3 Pg. 801-14 (Feb 25 2005) ISSN: 0022-2836 [Print] Netherlands
• PMID: 15713464 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Helminth
• Chemotactic Factors
• DNA, Helminth
• Helminth Proteins
• Ligands
• Macrophage-1 Antigen
• Vaccines
• Peptide Hydrolases

Topics

• Amino Acid Sequence
• Animals
• Antigens, Helminth (chemistry, genetics)
• Base Sequence
• Binding Sites
• Chemotactic Factors (chemistry)
• Cloning, Molecular
• Crystallography, X-Ray
• DNA, Helminth (genetics)
• Helminth Proteins (chemistry, genetics, immunology)
• Humans
• Ligands
• Macrophage-1 Antigen (metabolism)
• Models, Molecular
• Molecular Mimicry
• Molecular Sequence Data
• Molecular Weight
• Necator americanus (genetics, immunology, pathogenicity)
• Necatoriasis (immunology, prevention & control)
• Peptide Hydrolases (chemistry, genetics, immunology)
• Protein Conformation
• Sequence Homology, Amino Acid
• Static Electricity
• Vaccines (chemistry, genetics)