Structures of the mycobacterial MmpL4 and MmpL5 transporters provide insights into their role in siderophore export and iron acquisition.

IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences PLoS Biology Pub Date : 2024-10-18 eCollection Date: 2024-10-01 DOI:10.1371/journal.pbio.3002874
Rakesh Maharjan, Zhemin Zhang, Philip A Klenotic, William D Gregor, Marios L Tringides, Meng Cui, Georgiana E Purdy, Edward W Yu
{"title":"Structures of the mycobacterial MmpL4 and MmpL5 transporters provide insights into their role in siderophore export and iron acquisition.","authors":"Rakesh Maharjan, Zhemin Zhang, Philip A Klenotic, William D Gregor, Marios L Tringides, Meng Cui, Georgiana E Purdy, Edward W Yu","doi":"10.1371/journal.pbio.3002874","DOIUrl":null,"url":null,"abstract":"<p><p>The Mycobacterium tuberculosis (Mtb) pathogen, the causative agent of the airborne infection tuberculosis (TB), harbors a number of mycobacterial membrane protein large (MmpL) transporters. These membrane proteins can be separated into 2 distinct subclasses, where they perform important functional roles, and thus, are considered potential drug targets to combat TB. Previously, we reported both X-ray and cryo-EM structures of the MmpL3 transporter, providing high-resolution structural information for this subclass of the MmpL proteins. Currently, there is no structural information available for the subclass associated with MmpL4 and MmpL5, transporters that play a critical role in iron homeostasis of the bacterium. Here, we report cryo-EM structures of the M. smegmatis MmpL4 and MmpL5 transporters to resolutions of 2.95 Å and 3.00 Å, respectively. These structures allow us to propose a plausible pathway for siderophore translocation via these 2 transporters, an essential step for iron acquisition that enables the survival and replication of the mycobacterium.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 10","pages":"e3002874"},"PeriodicalIF":9.8000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524445/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"PLoS Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1371/journal.pbio.3002874","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"Agricultural and Biological Sciences","Score":null,"Total":0}
引用次数: 0

Abstract

The Mycobacterium tuberculosis (Mtb) pathogen, the causative agent of the airborne infection tuberculosis (TB), harbors a number of mycobacterial membrane protein large (MmpL) transporters. These membrane proteins can be separated into 2 distinct subclasses, where they perform important functional roles, and thus, are considered potential drug targets to combat TB. Previously, we reported both X-ray and cryo-EM structures of the MmpL3 transporter, providing high-resolution structural information for this subclass of the MmpL proteins. Currently, there is no structural information available for the subclass associated with MmpL4 and MmpL5, transporters that play a critical role in iron homeostasis of the bacterium. Here, we report cryo-EM structures of the M. smegmatis MmpL4 and MmpL5 transporters to resolutions of 2.95 Å and 3.00 Å, respectively. These structures allow us to propose a plausible pathway for siderophore translocation via these 2 transporters, an essential step for iron acquisition that enables the survival and replication of the mycobacterium.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
霉菌 MmpL4 和 MmpL5 转运体的结构揭示了它们在苷酸输出和铁获取中的作用。
结核分枝杆菌(Mtb)病原体是通过空气传播的结核病(TB)的致病菌,它携带有许多分枝杆菌膜蛋白大(MmpL)转运体。这些膜蛋白可分为两个不同的亚类,它们在其中发挥着重要的功能作用,因此被认为是抗击结核病的潜在药物靶标。此前,我们报道了 MmpL3 转运体的 X 射线和低温电子显微镜结构,为该亚类 MmpL 蛋白提供了高分辨率的结构信息。目前,还没有与 MmpL4 和 MmpL5 相关的亚类的结构信息,这些转运体在细菌的铁平衡中发挥着关键作用。在此,我们报告了 M. smegmatis MmpL4 和 MmpL5 转运体的低温电子显微镜结构,其分辨率分别为 2.95 Å 和 3.00 Å。通过这些结构,我们提出了通过这两个转运体进行苷酸转运的合理途径,而苷酸转运是获得铁的一个重要步骤,可使分枝杆菌得以生存和复制。
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 去求助
来源期刊
PLoS Biology
PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY
CiteScore
15.40
自引率
2.00%
发文量
359
审稿时长
3-8 weeks
期刊介绍: PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions. The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public. PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
期刊最新文献
Correction: Dog-human vocal interactions match dogs' sensory-motor tuning. Thalamic spindles and Up states coordinate cortical and hippocampal co-ripples in humans. Trajectories of human brain functional connectome maturation across the birth transition. Dopamine neurons that inform Drosophila olfactory memory have distinct, acute functions driving attraction and aversion. Excess mortality of infected ectotherms induced by warming depends on pathogen kingdom and evolutionary history.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1