Native structure of mosquito salivary protein uncovers domains relevant to pathogen transmission

Female mosquitoes inject saliva into vertebrate hosts during blood feeding. This process transmits mosquito-borne human pathogens that collectively cause similar to 1,000,000 deaths/year. Among the most abundant and conserved proteins secreted by female salivary glands is a high-molecular weight protein called salivary gland surface protein 1 (SGS1) that facilitates pathogen transmission, but its mechanism remains elusive. Here, we determine the native structure of SGS1 by the cryoID approach, showing that the 3364 amino-acid protein has a Tc toxin-like Rhs/YD shell, four receptor domains, and a set of C-terminal daisy-chained helices. These helices are partially shielded inside the Rhs/YD shell and poised to transform into predicted transmembrane helices. This transformation, and the numerous receptor domains on the surface of SGS1, are likely key in facilitating sporozoite/arbovirus invasion into the salivary glands and manipulating the host's immune response.

Automated summary

Female mosquitoes transmit mosquito-borne human pathogens that cause approximately 1,000,000 deaths/year by injecting saliva into vertebrate hosts during blood feeding. Salivary gland surface protein 1 (SGS1), a highly conserved protein secreted by female mosquitoes, plays a crucial role in pathogen transmission. By determining the native structure of SGS1, this study reveals its Tc toxin-like Rhs/YD shell, multiple receptor domains, and transformative potential of its C-terminal helices. Understanding the mechanism of SGS1 could provide insights into sporozoite/arbovirus invasion into salivary glands and manipulation of the host's immune response.