3NSW

Crystal Structure of Ancylostoma ceylanicum Excretory-Secretory Protein 2

Summary for 3NSW

• Entry DOI: 10.2210/pdb3nsw/pdb
• Descriptor: Excretory-secretory protein 2, (4S)-2-METHYL-2,4-PENTANEDIOL, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: ancylostoma ceylanicum, hookworm, excretory-secretory protein, merohedral twinning, immunomodulator, netrin domain, immune system
• Biological source: Ancylostoma ceylanicum
• Total number of polymer chains: 7
• Total formula weight: 84941.08

Authors

Kucera, K.,Modis, Y. (deposition date: 2010-07-02, release date: 2011-05-18, Last modification date: 2024-11-20)

Primary citation

Kucera, K.,Harrison, L.M.,Cappello, M.,Modis, Y.
Ancylostoma ceylanicum Excretory-Secretory Protein 2 Adopts a Netrin-Like Fold and Defines a Novel Family of Nematode Proteins.
J.Mol.Biol., 408:9-17, 2011

PubMed Abstract: Hookworms are human parasites that have devastating effects on global health, particularly in underdeveloped countries. Ancylostoma ceylanicum infects humans and animals, making it a useful model organism to study disease pathogenesis. A. ceylanicum excretory-secretory protein 2 (AceES-2), a highly immunoreactive molecule secreted by adult worms at the site of intestinal attachment, is partially protective when administered as a mucosal vaccine against hookworm anemia. The crystal structure of AceES-2 determined at 1.75 Å resolution shows that it adopts a netrin-like fold similar to that found in tissue inhibitors of matrix metalloproteases (TIMPs) and in complement factors C3 and C5. However, recombinant AceES-2 does not significantly inhibit the 10 most abundant human matrix metalloproteases or complement-mediated cell lysis. The presence of a highly acidic surface on AceES-2 suggests that it may function as a cytokine decoy receptor. Several small nematode proteins that have been annotated as TIMPs or netrin-domain-containing proteins display sequence homology in structurally important regions of AceES-2's netrin-like fold. Together, our results suggest that AceES-2 defines a novel family of nematode netrin-like proteins, which may function to modulate the host immune response to hookworm and other parasites.

PubMed: 21352830
DOI: 10.1016/j.jmb.2011.02.033

Experimental method

X-RAY DIFFRACTION (1.75 Å)