First Crystal Structure of Na-ASP-1, a Two-Domain Cap (Cysteine-Rich Secretory Protein / Antigen 5 / Pathogenesis Related-1) protein

Abstract

The major proteins secreted by the infective larval stage hookworms upon host entry, are Ancylostoma secreted proteins (ASPs) which are characterized by one or two CAP (cysteine-rich secretory protein / antigen 5 / pathogenesis related-1) domains. The CAP domain has been reported in a diversity of proteins unrelated by phylogeny and isolated from bacteria, plants, as well as animals but it has no confirmed function. The first structure of a two-CAP domain protein, Na-ASP-1, from the major human hookworm parasite Necator americanus was refined to a resolution limit of 2.2 Å. The structure reveals two CAP domains linked by a short loop. Overall the carboxyl terminus CAP domain is more similar structurally to one-domain ASPs than to the amino terminus CAP domain. This first structure of a two-domain CAP is a useful template for the homology modeling of other two-domain CAP proteins.