Mechanosensitive ion channels are essential for sensing and converting mechanical forces into electrical or chemical signals.These channels are widely distributed across bacteria,animals,and plants.In Arabidopsis thal...Mechanosensitive ion channels are essential for sensing and converting mechanical forces into electrical or chemical signals.These channels are widely distributed across bacteria,animals,and plants.In Arabidopsis thaliana,the OSCA family has been identified as mechanically activated ion channels that respond to osmotic stress by allowing calcium ions to enter the cell.This influx increases the cytoplasmic calcium concentration,triggering osmotic stress-induced signal transduction cascades in plants.In this study,we determined the structures of OSCA2.2 and OSCA3.1 via cryoelectron microscopy(cryo-EM).Both proteins form homodimers consisting of 11 transmembrane helices(TM1–11).The ion conduction pathway is formed by TM4–8.Despite belonging to the same family,OSCA2.2 and OSCA3.1 exhibit notable structural variations.Structural analysis revealed that both OSCA2.2 and OSCA3.1 exhibit a closed conformation.We also conducted functional studies on OSCA proteins via electrophysiological experiments and confirmed the role of key amino acids in the process of ion permeation.展开更多
The acetylpolyamine oxidase(APAO),spermine oxidase(SMO),and spermidine/spermine N1-acetyltransferase(SSAT)are pivotal enzymes in polyamine metabolism,exerting direct influence on polyamine homeostasis regulation.Dysfu...The acetylpolyamine oxidase(APAO),spermine oxidase(SMO),and spermidine/spermine N1-acetyltransferase(SSAT)are pivotal enzymes in polyamine metabolism,exerting direct influence on polyamine homeostasis regulation.Dysfunctions in these enzymes are intricately linked to inflammatory diseases and cancers.Establishing their three-dimensional structures is essential for exploring enzymatic catalytic mechanisms and designing inhibitors at the atomic level.This article primarily assesses the precision of AlphaFold2 and molecular dynamics simulations in determining the three-dimensional structures of these enzymes,utilizing protein conformation rationality assessment,residue correlation matrix,and other techniques.This provides robust models for subsequent polyamine catabolic metabolism calculations and offers valuable insights for modeling proteins that have yet to acquire crystal structures.展开更多
基金supported by the National Natural Science Foundation of China(32322041,W2412029,32321001,32471279)USTC Research Funds of the Double First-Class Initiative(YD9100002004,YD9100002020)+2 种基金Fundamental Research Funds for the Central Universities(WK9100000031)Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYPY20230034)the Natural Science Foundation of Anhui Province(2408085JX005).
文摘Mechanosensitive ion channels are essential for sensing and converting mechanical forces into electrical or chemical signals.These channels are widely distributed across bacteria,animals,and plants.In Arabidopsis thaliana,the OSCA family has been identified as mechanically activated ion channels that respond to osmotic stress by allowing calcium ions to enter the cell.This influx increases the cytoplasmic calcium concentration,triggering osmotic stress-induced signal transduction cascades in plants.In this study,we determined the structures of OSCA2.2 and OSCA3.1 via cryoelectron microscopy(cryo-EM).Both proteins form homodimers consisting of 11 transmembrane helices(TM1–11).The ion conduction pathway is formed by TM4–8.Despite belonging to the same family,OSCA2.2 and OSCA3.1 exhibit notable structural variations.Structural analysis revealed that both OSCA2.2 and OSCA3.1 exhibit a closed conformation.We also conducted functional studies on OSCA proteins via electrophysiological experiments and confirmed the role of key amino acids in the process of ion permeation.
基金National Natural Science Foundation of China(22073023)Natural Science Foundation of Henan Province(242300421134)+1 种基金the Young Backbone Teacher in Colleges and Universities of Henan Province(2021GGJS020)Foundation of State Key Laboratory of Antiviral Drugs。
文摘The acetylpolyamine oxidase(APAO),spermine oxidase(SMO),and spermidine/spermine N1-acetyltransferase(SSAT)are pivotal enzymes in polyamine metabolism,exerting direct influence on polyamine homeostasis regulation.Dysfunctions in these enzymes are intricately linked to inflammatory diseases and cancers.Establishing their three-dimensional structures is essential for exploring enzymatic catalytic mechanisms and designing inhibitors at the atomic level.This article primarily assesses the precision of AlphaFold2 and molecular dynamics simulations in determining the three-dimensional structures of these enzymes,utilizing protein conformation rationality assessment,residue correlation matrix,and other techniques.This provides robust models for subsequent polyamine catabolic metabolism calculations and offers valuable insights for modeling proteins that have yet to acquire crystal structures.
