Structural and Inhibitory Effects of Hinge Loop Mutagenesis in Serpin-2 from the Malaria Vector Anopheles gambiae

Zhang, Xin; Meekins, David A.; An, Chunju; Żółkiewski, Michał; Battaile, Kevin P.; Kanost, Michael R.; Lovell, Scott; Michel, Kristin

doi:10.1074/jbc.m114.625665

Cited by 6 publications

(5 citation statements)

References 74 publications

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“…To understand its function, three SRPN2 mutants containing either constitutively expelled or inserted hinge regions were developed, their structures were solved, and their activity against CLIPB9 was measured. SRPN2 hinge expulsion did not significantly increase CLIPB9 inhibition, but stable hinge insertion did not decrease the rate of RCL cleavage [147]. These data suggest the SRPN2 hinge insertion represents a molecular trade-off between RCL accessibility and rapid formation of the inhibitory complex, since the partial insertion provides an advantage towards complete RCL insertion following cleavage.…”

Section: Structure/function Aspects Of Arthropod Serpinsmentioning

confidence: 99%

Serpins in arthropod biology

Meekins

Kanost

Michel

2017

Seminars in Cell & Developmental Biology

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142

136

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Serpins are the largest known family of serine proteinase inhibitors and perform a variety of physiological functions in arthropods. Herein, we review the field of serpins in arthropod biology, providing an overview of current knowledge and topics of interest. Serpins regulate insect innate immunity via inhibition of serine proteinase cascades that initiate immune responses such as melanization and antimicrobial peptide production. In addition, several serpins with anti-pathogen activity are expressed as acute-phase serpins in insects upon infection. Parasitoid wasps can downregulate host serpin expression to modulate the host immune system. In addition, examples of serpin activity in development and reproduction in Drosophila have also been discovered. Serpins also function in host-pathogen interactions beyond immunity as constituents of venom in parasitoid wasps and saliva of blood-feeding ticks and mosquitoes. These serpins have distinct effects on immunosuppression and anticoagulation and are of interest for vaccine development. Lastly, the known structures of arthropod serpins are discussed, which represent the serpin inhibitory mechanism and provide a detailed overview of the process.

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Section: Structure/function Aspects Of Arthropod Serpinsmentioning

confidence: 99%

Serpins in arthropod biology

Meekins

Kanost

Michel

2017

Seminars in Cell & Developmental Biology

Self Cite

142

136

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“…Serine proteinase inhibitors, widely distributed in organisms, play key roles in a variety of biochemical pathways including hemolymph coagulation, PPO activation and antimicrobial synthesis. To date, many studies of serpins have been published in insects including B. mori , 52 , 53 , 54 M. sexta , 30 , 31 , 55 , 56 , 57 , 58 , 59 Mythimnan unipuncta , 60 A. gambiae , 61 , 62 D. melanogaste , 63 T. molitor 27 , 29 and O. furnaca lis. 64 Serpin‐derived from hymenopteran parasitoid has not been extensively studied.…”

Section: Discussionmentioning

confidence: 99%

A serpin (CvT‐serpin15) of teratocytes contributes to microbial‐resistance in Plutella xylostella during Cotesia vestalis parasitism

Zhou

et al. 2021

Pest Management Science

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BACKGROUND Parasitic wasps are an important group of entomophagous insects for pest control. As parasitic wasps often lay eggs on or into their associated hosts, parasitoids evolve to utilize several factors including venom, polydnavirus (PDV) to alter host physiology for successful parasitism. Some taxa of endoparasitoids produce teratocytes, which are a type of cell that is released into host insects when wasp eggs hatch. Teratocytes display multifunction in parasitism such as host nutritional exploration, immune and developmental regulation, by secreting plenty of proteins into host hemocoel. RESULTS A serpin (CvT‐serpin15) secreted by teratocytes was characterized. QPCR results showed the expressional level of CvT‐serpin15 was upregulated following bacterial challenges. Enzyme activity experiment indicated the recombinant CvT‐serpin15 protein could interfere with the growth of Gram‐positive bacteria Staphylococcus aureus. The survival rate assay demonstrated CvT‐serpin15 increased survival rate of Plutella xylostella infected by S. aureus. CONCLUSION CvT‐serpin15 secreted by teratocytes would boost the host immune system when pathogens invade host hemocoel during parasitism, and ultimately protect the development of wasp larva from bacterial infection. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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“…The PPOs are activated by proteolytic cleavage via an enzymatic cascade of serine proteases. This process requires complex interactions of different members in the CLIPs B, C, and A as well as serpins (An et al, 2011;Gulley et al, 2013;Povelones et al, 2013;Zhang et al, 2015;Cao et al, 2017;He et al, 2017;Meekins et al, 2017;Nakhleh et al, 2017;El Moussawi et al, 2019;Sousa et al, 2020). It has been shown recently that microbial melanization can be triggered by E. coli infection (Sousa et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Trained Immunity in Anopheles gambiae: Antibacterial Immunity Is Enhanced by Priming via Sugar Meal Supplemented With a Single Gut Symbiotic Bacterial Strain

et al. 2021

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Mosquitoes have evolved an effective innate immune system. The mosquito gut accommodates various microbes, which play a crucial role in shaping the mosquito immune system during evolution. The resident bacteria in the gut microbiota play an essential role in priming basal immunity. In this study, we show that antibacterial immunity in Anopheles gambiae can be enhanced by priming via a sugar meal supplemented with bacteria. Serratia fonticola S1 and Enterobacter sp. Ag1 are gut bacteria in mosquitoes. The intrathoracic injection of the two bacteria can result in an acute hemocoelic infection in the naïve mosquitoes with mortality of ∼40% at 24 h post-infection. However, the Enterobacter orSerratia primed mosquitoes showed a better 24 h survival upon the bacterial challenge. The priming confers the protection with a certain degree of specificity, the Enterobacter primed mosquitoes had a better survival upon the Enterobacter but not Serratia challenge, and the Serratia primed mosquitoes had a better survival upon the Serratia but not Enterobacter challenge. To understand the priming-mediated immune enhancement, the transcriptomes were characterized in the mosquitoes of priming as well as priming plus challenges. The RNA-seq was conducted to profile 10 transcriptomes including three samples of priming conditions (native microbiota, Serratia priming, and Enterobacter priming), six samples of priming plus challenges with the two bacteria, and one sample of injury control. The three priming regimes resulted in distinctive transcriptomic profiles with about 60% of genes affected by both bacteria. Upon challenges, different primed mosquitoes displayed different transcriptomic patterns in response to different bacteria. When a primed cohort was challenged with a heterogenous bacterium, more responsive genes were observed than when challenged with a homogenous bacterium. As expected, many canonical immune genes were responsive to the priming and challenge, but much more non-immune genes with various functions were also responsive in the contexts, which implies that the prior priming triggers a delicately coordinated systemic regulation that results in an enhanced immunity against the subsequent challenge. Besides the participation of typical immune pathways, the transcriptome data suggest the involvement of lysosome and metabolism in the context. Overall, this study demonstrated a trained immunity via priming with bacteria in diet.

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Structural and Inhibitory Effects of Hinge Loop Mutagenesis in Serpin-2 from the Malaria Vector Anopheles gambiae

Cited by 6 publications

References 74 publications

Serpins in arthropod biology

Serpins in arthropod biology

A serpin (CvT‐serpin15) of teratocytes contributes to microbial‐resistance in Plutella xylostella during Cotesia vestalis parasitism

Trained Immunity in Anopheles gambiae: Antibacterial Immunity Is Enhanced by Priming via Sugar Meal Supplemented With a Single Gut Symbiotic Bacterial Strain

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