Objective:To isolate a potassium ion channel Kv4.1 inhibitor from centipede venom,and to determine its sequence and structure.Methods:Ion-exchange chromatography and reversed-phase high-performance liquid chromatography were performed to separate and purify peptide components of centipede venom,and their inhibiting effect on Kv4.1 channel was determined by whole-cell patch clamp recording.The molecular weight of isolated peptide Kv4.1 channel inhibitor was identified with matrix assisted laser desorption ionization-time-of-flight mass spectrometry;its primary sequence was determined by Edman degradation sequencing and two-dimensional mass spectrometry;its structure was established based on iterative thread assembly refinement online analysis.Results:A peptide SsTx-P2 was separated from centipede venom with the molecular weight of 6122.8,and its primary sequence consists of 53 amino acid residues NH2-ELTWDFVRTCCKLFPDKSECTKACATEFTGGDESRLKDVWPRKLRSG DSRLKD-OH.Peptide SsTx-P2 potently inhibited the current of Kv4.1 channel transiently transfected in HEK293 cell,with 1.0 μmol/L SsTx-P2 suppressing 95%current of Kv4.1 channel.Its structure showed that SsTx-P2 shared a conserved helical structure.Conclusion:The study has isolated a novel peptide SsTx-P2 from centipede venom,which can potently inhibit the potassium ion channel Kv4.1 and displays structural conservation.

Objective:To isolate a potassium ion channel Kv4.1 inhibitor from centipede venom,and to determine its sequence and structure.Methods:Ion-exchange chromatography and reversed-phase high-performance liquid chromatography were performed to separate and purify peptide components of centipede venom,and their inhibiting effect on Kv4.1 channel was determined by whole-cell patch clamp recording.The molecular weight of isolated peptide Kv4.1 channel inhibitor was identified with matrix assisted laser desorption ionization-time-of-flight mass spectrometry;its primary sequence was determined by Edman degradation sequencing and two-dimensional mass spectrometry;its structure was established based on iterative thread assembly refinement online analysis.Results:A peptide SsTx-P2 was separated from centipede venom with the molecular weight of 6122.8,and its primary sequence consists of 53 amino acid residues NH2-ELTWDFVRTCCKLFPDKSECTKACATEFTGGDESRLKDVWPRKLRSG DSRLKD-OH.Peptide SsTx-P2 potently inhibited the current of Kv4.1 channel transiently transfected in HEK293 cell,with 1.0 μmol/L SsTx-P2 suppressing 95%current of Kv4.1 channel.Its structure showed that SsTx-P2 shared a conserved helical structure.Conclusion:The study has isolated a novel peptide SsTx-P2 from centipede venom,which can potently inhibit the potassium ion channel Kv4.1 and displays structural conservation.

Objective:To isolate a potassium ion channel Kv4.1 inhibitor from centipede venom,and to determine its sequence and structure.Methods:Ion-exchange chromatography and reversed-phase high-performance liquid chromatography were performed to separate and purify peptide components of centipede venom,and their inhibiting effect on Kv4.1 channel was determined by whole-cell patch clamp recording.The molecular weight of isolated peptide Kv4.1 channel inhibitor was identified with matrix assisted laser desorption ionization-time-of-flight mass spectrometry;its primary sequence was determined by Edman degradation sequencing and two-dimensional mass spectrometry;its structure was established based on iterative thread assembly refinement online analysis.Results:A peptide SsTx-P2 was separated from centipede venom with the molecular weight of 6122.8,and its primary sequence consists of 53 amino acid residues NH2-ELTWDFVRTCCKLFPDKSECTKACATEFTGGDESRLKDVWPRKLRSG DSRLKD-OH.Peptide SsTx-P2 potently inhibited the current of Kv4.1 channel transiently transfected in HEK293 cell,with 1.0 μmol/L SsTx-P2 suppressing 95%current of Kv4.1 channel.Its structure showed that SsTx-P2 shared a conserved helical structure.Conclusion:The study has isolated a novel peptide SsTx-P2 from centipede venom,which can potently inhibit the potassium ion channel Kv4.1 and displays structural conservation.

Objective:To isolate a potassium ion channel Kv4.1 inhibitor from centipede venom,and to determine its sequence and structure.Methods:Ion-exchange chromatography and reversed-phase high-performance liquid chromatography were performed to separate and purify peptide components of centipede venom,and their inhibiting effect on Kv4.1 channel was determined by whole-cell patch clamp recording.The molecular weight of isolated peptide Kv4.1 channel inhibitor was identified with matrix assisted laser desorption ionization-time-of-flight mass spectrometry;its primary sequence was determined by Edman degradation sequencing and two-dimensional mass spectrometry;its structure was established based on iterative thread assembly refinement online analysis.Results:A peptide SsTx-P2 was separated from centipede venom with the molecular weight of 6122.8,and its primary sequence consists of 53 amino acid residues NH2-ELTWDFVRTCCKLFPDKSECTKACATEFTGGDESRLKDVWPRKLRSG DSRLKD-OH.Peptide SsTx-P2 potently inhibited the current of Kv4.1 channel transiently transfected in HEK293 cell,with 1.0 μmol/L SsTx-P2 suppressing 95%current of Kv4.1 channel.Its structure showed that SsTx-P2 shared a conserved helical structure.Conclusion:The study has isolated a novel peptide SsTx-P2 from centipede venom,which can potently inhibit the potassium ion channel Kv4.1 and displays structural conservation.

Objective:To isolate a potassium ion channel Kv4.1 inhibitor from centipede venom,and to determine its sequence and structure.Methods:Ion-exchange chromatography and reversed-phase high-performance liquid chromatography were performed to separate and purify peptide components of centipede venom,and their inhibiting effect on Kv4.1 channel was determined by whole-cell patch clamp recording.The molecular weight of isolated peptide Kv4.1 channel inhibitor was identified with matrix assisted laser desorption ionization-time-of-flight mass spectrometry;its primary sequence was determined by Edman degradation sequencing and two-dimensional mass spectrometry;its structure was established based on iterative thread assembly refinement online analysis.Results:A peptide SsTx-P2 was separated from centipede venom with the molecular weight of 6122.8,and its primary sequence consists of 53 amino acid residues NH2-ELTWDFVRTCCKLFPDKSECTKACATEFTGGDESRLKDVWPRKLRSG DSRLKD-OH.Peptide SsTx-P2 potently inhibited the current of Kv4.1 channel transiently transfected in HEK293 cell,with 1.0 μmol/L SsTx-P2 suppressing 95%current of Kv4.1 channel.Its structure showed that SsTx-P2 shared a conserved helical structure.Conclusion:The study has isolated a novel peptide SsTx-P2 from centipede venom,which can potently inhibit the potassium ion channel Kv4.1 and displays structural conservation.

Objective:To isolate a potassium ion channel Kv4.1 inhibitor from centipede venom,and to determine its sequence and structure.Methods:Ion-exchange chromatography and reversed-phase high-performance liquid chromatography were performed to separate and purify peptide components of centipede venom,and their inhibiting effect on Kv4.1 channel was determined by whole-cell patch clamp recording.The molecular weight of isolated peptide Kv4.1 channel inhibitor was identified with matrix assisted laser desorption ionization-time-of-flight mass spectrometry;its primary sequence was determined by Edman degradation sequencing and two-dimensional mass spectrometry;its structure was established based on iterative thread assembly refinement online analysis.Results:A peptide SsTx-P2 was separated from centipede venom with the molecular weight of 6122.8,and its primary sequence consists of 53 amino acid residues NH2-ELTWDFVRTCCKLFPDKSECTKACATEFTGGDESRLKDVWPRKLRSG DSRLKD-OH.Peptide SsTx-P2 potently inhibited the current of Kv4.1 channel transiently transfected in HEK293 cell,with 1.0 μmol/L SsTx-P2 suppressing 95%current of Kv4.1 channel.Its structure showed that SsTx-P2 shared a conserved helical structure.Conclusion:The study has isolated a novel peptide SsTx-P2 from centipede venom,which can potently inhibit the potassium ion channel Kv4.1 and displays structural conservation.

Objective:To isolate a potassium ion channel Kv4.1 inhibitor from centipede venom,and to determine its sequence and structure.Methods:Ion-exchange chromatography and reversed-phase high-performance liquid chromatography were performed to separate and purify peptide components of centipede venom,and their inhibiting effect on Kv4.1 channel was determined by whole-cell patch clamp recording.The molecular weight of isolated peptide Kv4.1 channel inhibitor was identified with matrix assisted laser desorption ionization-time-of-flight mass spectrometry;its primary sequence was determined by Edman degradation sequencing and two-dimensional mass spectrometry;its structure was established based on iterative thread assembly refinement online analysis.Results:A peptide SsTx-P2 was separated from centipede venom with the molecular weight of 6122.8,and its primary sequence consists of 53 amino acid residues NH2-ELTWDFVRTCCKLFPDKSECTKACATEFTGGDESRLKDVWPRKLRSG DSRLKD-OH.Peptide SsTx-P2 potently inhibited the current of Kv4.1 channel transiently transfected in HEK293 cell,with 1.0 μmol/L SsTx-P2 suppressing 95%current of Kv4.1 channel.Its structure showed that SsTx-P2 shared a conserved helical structure.Conclusion:The study has isolated a novel peptide SsTx-P2 from centipede venom,which can potently inhibit the potassium ion channel Kv4.1 and displays structural conservation.

Objective:To isolate a potassium ion channel Kv4.1 inhibitor from centipede venom,and to determine its sequence and structure.Methods:Ion-exchange chromatography and reversed-phase high-performance liquid chromatography were performed to separate and purify peptide components of centipede venom,and their inhibiting effect on Kv4.1 channel was determined by whole-cell patch clamp recording.The molecular weight of isolated peptide Kv4.1 channel inhibitor was identified with matrix assisted laser desorption ionization-time-of-flight mass spectrometry;its primary sequence was determined by Edman degradation sequencing and two-dimensional mass spectrometry;its structure was established based on iterative thread assembly refinement online analysis.Results:A peptide SsTx-P2 was separated from centipede venom with the molecular weight of 6122.8,and its primary sequence consists of 53 amino acid residues NH2-ELTWDFVRTCCKLFPDKSECTKACATEFTGGDESRLKDVWPRKLRSG DSRLKD-OH.Peptide SsTx-P2 potently inhibited the current of Kv4.1 channel transiently transfected in HEK293 cell,with 1.0 μmol/L SsTx-P2 suppressing 95%current of Kv4.1 channel.Its structure showed that SsTx-P2 shared a conserved helical structure.Conclusion:The study has isolated a novel peptide SsTx-P2 from centipede venom,which can potently inhibit the potassium ion channel Kv4.1 and displays structural conservation.

After decades of development,protein and peptide drugs have now grown into a major drug class in the marketplace.Target identification and validation are crucial for the discovery of protein and peptide drugs,and bioinformatics prediction of targets based on the characteristics of known target proteins will help improve the efficiency and success rate of target selection.However,owing to the developmental history in the pharmaceutical industry,previous systematic exploration of the target spaces has mainly focused on traditional small-molecule drugs,while studies related to protein and peptide drugs are lacking.Here,we systematically explore the target spaces in the human genome specifically for protein and peptide drugs.Compared with other proteins,both suc-cessful protein and peptide drug targets have many special characteristics,and are also significantly different from those of small-molecule drugs in many aspects.Based on these features,we develop separate effective genome-wide target prediction models for protein and peptide drugs.Finally,a user-friendly web server,Predictor Of Protein and Peptide drugs'therapeutic Targets(POPPIT)(http://poppit.ncpsb.org.cn/),is established,which provides not only target prediction specifically for protein and peptide drugs but also abundant annotations for predicted targets.

Genome-wide physical protein-protein interaction(PPI)mapping remains a major chal-lenge for current technologies.Here,we reported a high-efficiency BiFC-seq method,yeast-enhanced green fluorescent protein-based bimolecular fluorescence complementation(yEGFP-BiFC)coupled with next-generation DNA sequencing,for interactome mapping.We first applied yEGFP-BiFC method to systematically investigate an intraviral network of the Ebola virus.Two-thirds(9/14)of known interactions of EBOV were recaptured,and five novel interactions were discovered.Next,we used the BiFC-seq method to map the interactome of the tumor protein p53.We identified 97 interactors of p53,more than three-quarters of which were novel.Furthermore,in a more complex background,we screened potential interactors by pooling two BiFC libraries together and revealed a network of 229 interactions among 205 proteins.These results show that BiFC-seq is a highly sensitive,rapid,and economical method for genome-wide interactome map-ping.