Conformational heterogeneity and structural features for function of the prototype viroporin influenza AM2

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Kyriakos Georgiou, Antonios Kolocouris
{"title":"Conformational heterogeneity and structural features for function of the prototype viroporin influenza AM2","authors":"Kyriakos Georgiou,&nbsp;Antonios Kolocouris","doi":"10.1016/j.bbamem.2024.184387","DOIUrl":null,"url":null,"abstract":"<div><div>The 97-residue influenza A matrix 2 (ΑM2) protein, a prototype for viroporins, transports protons through water molecules and His37. We discuss structural biology and molecular biophysics experiments and some functional assays that have transformed over 40 years our understanding of the structure and function of AM2. The structural studies on ΑM2 have been performed with different conditions (pH, temperature, lipid, constructs) and using various protein constructs, e.g., AM2 transmembrane (AM2TM) domain, AM2 conductance domain (AM2CD), ectodomain-containing or ectodomain-truncated, AM2 full length (AM2FL) and aimed to describe the different conformations and structural details that are necessary for the stability and function of AM2. However, the conclusions from these experiments appeared sometimes ambiguous and caused exciting debates. This was not due to inaccurate measurements, but instead because of the different membrane mimetic environment used, e.g., detergent, micelles or phospholipid bilayer, the method (e.g., X-ray crystallography, solid state NMR, solution NMR, native mass spectrometry), the used protein construct (e.g., AM2TM or AM2CD), or the amino acids residues to follow observables (e.g., NMR chemical shifts). We present these results according to the different used biophysical methods, the research groups and often by keeping a chronological order for presenting the progress in the research. We discuss ideas for additional research on structural details of AM2 and how the present findings can be useful to explore new routes of influenza A inhibition. The AM2 research can provide inspiration to study other viroporins as drug targets.</div></div>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0005273624001184","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0

Abstract

The 97-residue influenza A matrix 2 (ΑM2) protein, a prototype for viroporins, transports protons through water molecules and His37. We discuss structural biology and molecular biophysics experiments and some functional assays that have transformed over 40 years our understanding of the structure and function of AM2. The structural studies on ΑM2 have been performed with different conditions (pH, temperature, lipid, constructs) and using various protein constructs, e.g., AM2 transmembrane (AM2TM) domain, AM2 conductance domain (AM2CD), ectodomain-containing or ectodomain-truncated, AM2 full length (AM2FL) and aimed to describe the different conformations and structural details that are necessary for the stability and function of AM2. However, the conclusions from these experiments appeared sometimes ambiguous and caused exciting debates. This was not due to inaccurate measurements, but instead because of the different membrane mimetic environment used, e.g., detergent, micelles or phospholipid bilayer, the method (e.g., X-ray crystallography, solid state NMR, solution NMR, native mass spectrometry), the used protein construct (e.g., AM2TM or AM2CD), or the amino acids residues to follow observables (e.g., NMR chemical shifts). We present these results according to the different used biophysical methods, the research groups and often by keeping a chronological order for presenting the progress in the research. We discuss ideas for additional research on structural details of AM2 and how the present findings can be useful to explore new routes of influenza A inhibition. The AM2 research can provide inspiration to study other viroporins as drug targets.

Abstract Image

原型病毒蛋白流感 AM2 功能的构象异质性和结构特征。
97个残基的甲型流感基质2(ΑM2)蛋白是病毒蛋白的原型,它通过水分子和His37转运质子。我们讨论了结构生物学和分子生物物理学实验以及一些功能测定,这些实验和测定在过去 40 年中改变了我们对 AM2 结构和功能的理解。对ΑM2的结构研究是在不同条件(pH值、温度、脂质、构建体)下进行的,并使用了不同的蛋白质构建体,如AM2跨膜(AM2TM)结构域、AM2传导结构域(AM2CD)、含外结构域或外结构域截断、AM2全长(AM2FL),旨在描述AM2稳定性和功能所必需的不同构象和结构细节。然而,这些实验的结论有时显得模棱两可,引起了激烈的争论。这并不是因为测量结果不准确,而是因为使用了不同的膜模拟环境,如去垢剂、胶束或磷脂双分子层,使用了不同的方法(如 X 射线晶体学、固态核磁共振、溶液核磁共振、原生质谱),构建了不同的蛋白质(如 AM2TM 或 AM2CD),或跟踪了不同的氨基酸残基。我们根据所使用的不同生物物理方法、研究小组来介绍这些成果,并通常按照时间顺序介绍研究进展。我们讨论了对 AM2 结构细节进行更多研究的想法,以及目前的发现如何有助于探索抑制甲型流感的新途径。AM2的研究可以为研究其他作为药物靶点的病毒蛋白提供灵感。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信