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Recognition of Aedes aegypti Mosquito Saliva Protein LTRIN by the Human Receptor LTβR for Controlling the Immune Response

Authors :
Su Ning Loh
Ian Russell Anthony
Edem Gavor
Xin Shan Lim
R. Manjunatha Kini
Yu Keung Mok
J. Sivaraman
Source :
Biology, Vol 13, Iss 1, p 42 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Salivary proteins from mosquitoes have received significant attention lately due to their potential to develop therapeutic treatments or vaccines for mosquito-borne diseases. Here, we report the characterization of LTRIN (lymphotoxin beta receptor inhibitor), a salivary protein known to enhance the pathogenicity of ZIKV by interrupting the LTβR-initiated NF-κB signaling pathway and, therefore, diminish the immune responses. We demonstrated that the truncated C-terminal LTRIN (ΔLTRIN) is a dimeric protein with a stable alpha helix-dominant secondary structure, which possibly aids in withstanding the temperature fluctuations during blood-feeding events. ΔLTRIN possesses two Ca2+ binding EF-hand domains, with the second EF-hand motif playing a more significant role in interacting with LTβR. Additionally, we mapped the primary binding regions of ΔLTRIN on LTβR using hydrogen–deuterium exchange mass spectrometry (HDX-MS) and identified that 91QEKAHIAEHMDVPIDTSKMSEQELQFHY118 from the N-terminal of ΔLTRIN is the major interacting region. Together, our studies provide insight into the recognition of LTRIN by LTβR. This finding may aid in a future therapeutic and transmission-blocking vaccine development against ZIKV.

Details

Language :
English
ISSN :
13010042 and 20797737
Volume :
13
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.9b48eb185704940bbb4e0572f24009c
Document Type :
article
Full Text :
https://doi.org/10.3390/biology13010042