Xiao-Xuan Shi, Si-Kao Guo, Pengye Wang, Hong Chen, P. Xie
{"title":"全原子分子动力学模拟揭示了动力学蛋白如何从一个头结合状态过渡到两个头结合状态","authors":"Xiao-Xuan Shi, Si-Kao Guo, Pengye Wang, Hong Chen, P. Xie","doi":"10.1002/prot.25833","DOIUrl":null,"url":null,"abstract":"Kinesin dimer walks processively along a microtubule (MT) protofilament in a hand‐over‐hand manner, transiting alternately between one‐head‐bound (1HB) and two‐heads‐bound (2HB) states. In 1HB state, one head bound by adenosine diphosphate (ADP) is detached from MT and the other head is bound to MT. Here, using all‐atom molecular dynamics simulations we determined the position and orientation of the detached ADP‐head relative to the MT‐bound head in 1HB state. We showed that in 1HB state when the MT‐bound head is in ADP or nucleotide‐free state, with its neck linker being undocked, the detached ADP‐head and the MT‐bound head have the high binding energy, and after adenosine triphosphate (ATP) binds to the MT‐bound head, with its neck linker being docked, the binding energy between the two heads is reduced greatly. These results reveal how the kinesin dimer retains 1HB state before ATP binding and how the dimer transits from 1HB to 2HB state after ATP binding. Key residues involved in the head‐head interaction in 1HB state were identified.","PeriodicalId":20789,"journal":{"name":"Proteins: Structure","volume":"274 1","pages":"545 - 557"},"PeriodicalIF":0.0000,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"16","resultStr":"{\"title\":\"All‐atom molecular dynamics simulations reveal how kinesin transits from one‐head‐bound to two‐heads‐bound state\",\"authors\":\"Xiao-Xuan Shi, Si-Kao Guo, Pengye Wang, Hong Chen, P. Xie\",\"doi\":\"10.1002/prot.25833\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Kinesin dimer walks processively along a microtubule (MT) protofilament in a hand‐over‐hand manner, transiting alternately between one‐head‐bound (1HB) and two‐heads‐bound (2HB) states. In 1HB state, one head bound by adenosine diphosphate (ADP) is detached from MT and the other head is bound to MT. Here, using all‐atom molecular dynamics simulations we determined the position and orientation of the detached ADP‐head relative to the MT‐bound head in 1HB state. We showed that in 1HB state when the MT‐bound head is in ADP or nucleotide‐free state, with its neck linker being undocked, the detached ADP‐head and the MT‐bound head have the high binding energy, and after adenosine triphosphate (ATP) binds to the MT‐bound head, with its neck linker being docked, the binding energy between the two heads is reduced greatly. These results reveal how the kinesin dimer retains 1HB state before ATP binding and how the dimer transits from 1HB to 2HB state after ATP binding. Key residues involved in the head‐head interaction in 1HB state were identified.\",\"PeriodicalId\":20789,\"journal\":{\"name\":\"Proteins: Structure\",\"volume\":\"274 1\",\"pages\":\"545 - 557\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2020-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"16\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Proteins: Structure\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/prot.25833\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proteins: Structure","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/prot.25833","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
All‐atom molecular dynamics simulations reveal how kinesin transits from one‐head‐bound to two‐heads‐bound state
Kinesin dimer walks processively along a microtubule (MT) protofilament in a hand‐over‐hand manner, transiting alternately between one‐head‐bound (1HB) and two‐heads‐bound (2HB) states. In 1HB state, one head bound by adenosine diphosphate (ADP) is detached from MT and the other head is bound to MT. Here, using all‐atom molecular dynamics simulations we determined the position and orientation of the detached ADP‐head relative to the MT‐bound head in 1HB state. We showed that in 1HB state when the MT‐bound head is in ADP or nucleotide‐free state, with its neck linker being undocked, the detached ADP‐head and the MT‐bound head have the high binding energy, and after adenosine triphosphate (ATP) binds to the MT‐bound head, with its neck linker being docked, the binding energy between the two heads is reduced greatly. These results reveal how the kinesin dimer retains 1HB state before ATP binding and how the dimer transits from 1HB to 2HB state after ATP binding. Key residues involved in the head‐head interaction in 1HB state were identified.