Nikhil Maroli , Matthew J. Ryan , Martin T. Zanni , Alexei A. Kananenka
{"title":"K+ 通道中的选择性过滤羰基是否会从孔中翻转?二维红外光谱研究","authors":"Nikhil Maroli , Matthew J. Ryan , Martin T. Zanni , Alexei A. Kananenka","doi":"10.1016/j.yjsbx.2024.100108","DOIUrl":null,"url":null,"abstract":"<div><p>Molecular dynamics simulations revealed that the carbonyls of the Val residue in the conserved selectivity filter sequence TVGTG of potassium ion channels can flip away from the pore to form hydrogen bonds with the network of water molecules residing behind the selectivity filter. Such a configuration has been proposed to be relevant for C-type inactivation. Experimentally, X-ray crystallography of the KcsA channel admits the possibility that the Val carbonyls can flip, but it cannot decisively confirm the existence of such a configuration. In this study, we combined molecular dynamics simulations and line shape theory to design two-dimensional infrared spectroscopy experiments that can corroborate the existence of the selectivity filter configuration with flipped Val carbonyls. This ability to distinguish between flipped and unflipped carbonyls is based on the varying strength of the electric field inside and outside the pore, which is directly linked to carbonyl stretching frequencies that can be resolved using infrared spectroscopy.</p></div>","PeriodicalId":17238,"journal":{"name":"Journal of Structural Biology: X","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590152424000138/pdfft?md5=13bf2c257aaf33fbd68799a7ce5f4412&pid=1-s2.0-S2590152424000138-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Do selectivity filter carbonyls in K+ channels flip away from the pore? Two-dimensional infrared spectroscopy study\",\"authors\":\"Nikhil Maroli , Matthew J. Ryan , Martin T. Zanni , Alexei A. Kananenka\",\"doi\":\"10.1016/j.yjsbx.2024.100108\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Molecular dynamics simulations revealed that the carbonyls of the Val residue in the conserved selectivity filter sequence TVGTG of potassium ion channels can flip away from the pore to form hydrogen bonds with the network of water molecules residing behind the selectivity filter. Such a configuration has been proposed to be relevant for C-type inactivation. Experimentally, X-ray crystallography of the KcsA channel admits the possibility that the Val carbonyls can flip, but it cannot decisively confirm the existence of such a configuration. In this study, we combined molecular dynamics simulations and line shape theory to design two-dimensional infrared spectroscopy experiments that can corroborate the existence of the selectivity filter configuration with flipped Val carbonyls. This ability to distinguish between flipped and unflipped carbonyls is based on the varying strength of the electric field inside and outside the pore, which is directly linked to carbonyl stretching frequencies that can be resolved using infrared spectroscopy.</p></div>\",\"PeriodicalId\":17238,\"journal\":{\"name\":\"Journal of Structural Biology: X\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-07-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2590152424000138/pdfft?md5=13bf2c257aaf33fbd68799a7ce5f4412&pid=1-s2.0-S2590152424000138-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Structural Biology: X\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2590152424000138\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Structural Biology: X","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590152424000138","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
分子动力学模拟显示,在钾离子通道的保守选择性滤过序列 TVGTG 中,缬氨酸残基的羰基可以翻转离开孔道,与选择性滤过器后面的水分子网络形成氢键。这种构型被认为与 C 型失活有关。从实验角度来看,KcsA 通道的 X 射线晶体学研究承认缬氨酰羰基有可能翻转,但无法明确证实这种构型的存在。在本研究中,我们结合分子动力学模拟和线形理论设计了二维红外光谱实验,从而证实了具有翻转缬氨酰羰基的选择性过滤构型的存在。这种区分翻转羰基和未翻转羰基的能力是基于孔隙内外电场强度的变化,而电场强度与羰基伸展频率直接相关,可以通过红外光谱来分辨。
Do selectivity filter carbonyls in K+ channels flip away from the pore? Two-dimensional infrared spectroscopy study
Molecular dynamics simulations revealed that the carbonyls of the Val residue in the conserved selectivity filter sequence TVGTG of potassium ion channels can flip away from the pore to form hydrogen bonds with the network of water molecules residing behind the selectivity filter. Such a configuration has been proposed to be relevant for C-type inactivation. Experimentally, X-ray crystallography of the KcsA channel admits the possibility that the Val carbonyls can flip, but it cannot decisively confirm the existence of such a configuration. In this study, we combined molecular dynamics simulations and line shape theory to design two-dimensional infrared spectroscopy experiments that can corroborate the existence of the selectivity filter configuration with flipped Val carbonyls. This ability to distinguish between flipped and unflipped carbonyls is based on the varying strength of the electric field inside and outside the pore, which is directly linked to carbonyl stretching frequencies that can be resolved using infrared spectroscopy.