PUBLICATION

Identification of the zinc finger protein ZRANB2 as a novel maternal LPS-binding protein that protects embryos of zebrafish against Gram-negative bacterial infections

Authors
Wang, X., Du, X., Li, H., Zhang, S.
ID
ZDB-PUB-160108-4
Date
2016
Source
The Journal of biological chemistry   291(8): 4019-34 (Journal)
Registered Authors
Li, Hongyan
Keywords
LPS-binding protein, ZRANB2, bacteria, embryo, innate immunity, zebrafish, zinc
MeSH Terms
  • Aeromonas hydrophila/metabolism*
  • Animals
  • Carrier Proteins*/genetics
  • Carrier Proteins*/metabolism
  • Embryo, Nonmammalian*/metabolism
  • Embryo, Nonmammalian*/microbiology
  • Fish Diseases*/genetics
  • Fish Diseases*/metabolism
  • Gram-Negative Bacterial Infections*/embryology
  • Gram-Negative Bacterial Infections*/genetics
  • Gram-Negative Bacterial Infections*/microbiology
  • Gram-Negative Bacterial Infections*/veterinary
  • RNA-Binding Proteins/genetics
  • RNA-Binding Proteins/metabolism*
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Zebrafish*/microbiology
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
PubMed
26740623 Full text @ J. Biol. Chem.
Abstract
Zinc finger ZRANB2 proteins are widespread in animals, but their functions and mechanisms remain poorly defined. Here we clearly demonstrate that ZRANB2 is a newly-identified LPS-binding protein present abundantly in the eggs/embryos of zebrafish. We also show that recombinant ZRANB2 (rZRANB2) acts as a pattern recognition receptor capable of identifying the bacterial signature molecule LPS as well as binding the Gram-negative bacteria Escherichia coli, Vibrio anguilarum and Aeromonas hydrophila, and functions as an antibacterial effector molecule capable of directly killing the bacteria. Furthermore, we reveal that N-terminal 11-37 residues consisting of the first ZnF_RBZ domain are indispensable for ZRANB2 antimicrobial activity. Importantly, microinjection of rZRANB2 into early embryos significantly enhances the resistance of the embryos against pathogenic A. hydrophila challenge, and this enhanced bacterial resistance is markedly reduced by co-injection of anti-ZRANB2 antibody. Moreover, precipitation of ZRANB2 in the embryo extracts by the pre-incubation with anti-ZRANB2 antibody causes a marked decrease in the antibacterial activity of the extracts against the bacteria tested. In addition, the N-terminal peptides Z1/37 or Z11/37 with in vitro antibacterial activity also promote the resistance of embryos against A. hydrophila, but the peptide Z38/198 without in vitro antibacterial activity does not. Collectively, these indicate that ZRANB2 is a maternal LPS-binding protein which can protect the early embryos of zebrafish against pathogenic attacks, a novel role ever assigned to ZRANB2 proteins. This work also provides a new angle for insights into the immunological functions of zinc finger proteins that are widely distributed in various animals.
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