Improving Soluble Expression of SARS-CoV-2 Spike Priming Protease TMPRSS2 with an Artificial Fusing Protein.

Publication date: Jun 22, 2023

SARS-CoV-2 relies on the recognition of the spike protein by the host cell receptor ACE2 for cellular entry. In this process, transmembrane serine protease 2 (TMPRSS2) plays a pivotal role, as it acts as the principal priming agent catalyzing spike protein cleavage to initiate the fusion of the cell membrane with the virus. Thus, TMPRSS2 is an ideal pharmacological target for COVID-19 therapy development, and the effective production of high-quality TMPRSS2 protein is essential for basic and pharmacological research. Unfortunately, as a mammalian-originated protein, TMPRSS2 could not be solubly expressed in the prokaryotic system. In this study, we applied different protein engineering methods and found that an artificial protein XXA derived from an antifreeze protein can effectively promote the proper folding of TMPRSS2, leading to a significant improvement in the yield of its soluble form. Our study also showed that the fused XXA protein did not influence the enzymatic catalytic activity; instead, it greatly enhanced TMPRSS2’s thermostability. Therefore, our strategy for increasing TMPRSS2 expression would be beneficial for the large-scale production of this stable enzyme, which would accelerate aniti-SARS-CoV-2 therapeutics development.

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Concepts Keywords
Cleavage artificial protein
Mammalian protease
Principal protein expression
Therapeutics SARS-CoV-2


Type Source Name
disease IDO process
drug DRUGBANK Serine
disease MESH COVID-19
disease VO effective
disease IDO production
disease IDO quality
drug DRUGBANK Coenzyme M
disease IDO host
disease VO Viruses
drug DRUGBANK Angiotensin II
drug DRUGBANK Trestolone
drug DRUGBANK Amino acids
disease MESH inflammation
disease MESH tumor
disease IDO organism
disease MESH coronavirus infection
drug DRUGBANK Isopropyl beta-D-thiogalactopyranoside
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Albendazole
drug DRUGBANK (S)-Des-Me-Ampa
disease IDO assay
drug DRUGBANK Trypsin
drug DRUGBANK Imidazole
disease VO efficiency
disease MESH infectious diseases
drug DRUGBANK Honey
disease VO storage
disease VO USA
drug DRUGBANK Human Serum Albumin
drug DRUGBANK Formic Acid
drug DRUGBANK Flunarizine
drug DRUGBANK Tromethamine
disease IDO cell
disease VO Glycoprotein
disease MESH infection
disease MESH influenza
drug DRUGBANK Troleandomycin
drug DRUGBANK Guanosine
drug DRUGBANK Enzalutamide
disease VO gene
drug DRUGBANK Hydroxycitronellal
drug DRUGBANK Glutathione
disease VO Bacteria

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