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

di: Su Ning Loh, Ian Russell Anthony, Edem Gavor, Xin Shan Lim, R. Manjunatha Kini, Yu Keung Mok, J. Sivaraman

Natura: Article
Pubblicazione: MDPI AG 2024-01-01

Descrizione

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 Ca<sup>2+</sup> 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 <sup>91</sup>QEKAHIAEHMDVPIDTSKMSEQELQFHY<sup>118</sup> 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.