The mitochondrial respiratory complex II or succinate: ubiquinone oxidoreductase (SQR) is a key membrane complex in both the tricarboxylic acid cycle and aerobic respiration. Five disinfectant compounds were investigated with their potent inhibition effects on the ubiquinone reduction activity of the porcine mitochondrial SQR by enzymatic assay and crystallography. Crystal structure of the SQR bound with thiabendazole (TBZ) reveals a different inhibitor-binding feature at the ubiquinone binding site where a water molecule plays an important role. The obvious inhibitory effect of TBZ based on the biochemical data (IC(50) ~100 μmol/L) and the significant structure-based binding affinity calculation (~94 μmol/L) draw the suspicion of using TBZ as a good disinfectant compound for nematode infections treatment and fruit storage.
Animals ; Anthelmintics ; metabolism ; pharmacology ; Binding Sites ; Crystallography, X-Ray ; Electron Transport Complex II ; drug effects ; Inhibitory Concentration 50 ; Mitochondria ; drug effects ; enzymology ; Molecular Structure ; Oxidoreductases ; antagonists & inhibitors ; chemistry ; Structure-Activity Relationship ; Swine ; Thiabendazole ; chemistry ; metabolism ; pharmacology ; Ubiquinone ; antagonists & inhibitors ; Water ; chemistry ; metabolism

T cells play an essential role in adaptive immunity,and the specific recognition of antigens by T cell receptors(TCRs)is the key in initiating anti-tumor and antiviral immune responses.Recent studies have demonstrated that force plays an important regulatory role in T cell immune responses,laying the foundation for the emerging field of mechanoimmunology.In this review,the mechanisms by which force assists TCRs in distinguishing between specific antigens and non-specific antigens,as well as the critical role force plays in initiating TCR transmembrane signaling and triggering T cell activation are mainly discussed.The novel biophysical single-molecule tools and advanced imaging techniques that can deeply reveal the importance of mechanical forces at the molecular and/or cellular level are summarized.Based on the research results of domestic and foreign expert teams,combined with the research work of our team,this review summarizes and discusses the role of force in T cell function,so as to provide a system framework for deeply understanding the cutting-edge hotspots in the field of mechanoimunology and exploring new research directions.