• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

冷冻电镜结构的人带 3 转运蛋白表明涉及耦合运动的氯离子和碳酸氢根离子的运输机制。

Cryo-EM structures of the human band 3 transporter indicate a transport mechanism involving the coupled movement of chloride and bicarbonate ions.

机构信息

Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.

Department of Pharmaceutical Sciences, Northeastern University School of Pharmacy, Boston, Massachusetts, United States of America.

出版信息

PLoS Biol. 2024 Aug 21;22(8):e3002719. doi: 10.1371/journal.pbio.3002719. eCollection 2024 Aug.

DOI:10.1371/journal.pbio.3002719
PMID:39167625
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11338459/
Abstract

The band 3 transporter is a critical integral membrane protein of the red blood cell (RBC), as it is responsible for catalyzing the exchange of bicarbonate and chloride anions across the plasma membrane. To elucidate the structural mechanism of the band 3 transporter, detergent solubilized human ghost membrane reconstituted in nanodiscs was applied to a cryo-EM holey carbon grid to define its composition. With this approach, we identified and determined structural information of the human band 3 transporter. Here, we present 5 different cryo-EM structures of the transmembrane domain of dimeric band 3, either alone or bound with chloride or bicarbonate. Interestingly, we observed that human band 3 can form both symmetric and asymmetric dimers with a different combination of outward-facing (OF) and inward-facing (IF) states. These structures also allow us to obtain the first model of a human band 3 molecule at the IF conformation. Based on the structural data of these dimers, we propose a model of ion transport that is in favor of the elevator-type mechanism.

摘要

带 3 转运蛋白是红细胞（RBC）的一种重要的整合膜蛋白，因为它负责催化碳酸氢根和氯离子阴离子穿过质膜的交换。为了阐明带 3 转运蛋白的结构机制，用去污剂溶解的人幽灵膜在纳米盘中重建，然后应用于冷冻电镜有孔碳网格来确定其组成。通过这种方法，我们鉴定并确定了人带 3 转运蛋白的结构信息。在这里，我们展示了 5 种不同的二聚体带 3 跨膜结构域的冷冻电镜结构，要么单独存在，要么与氯离子或碳酸氢根结合。有趣的是，我们观察到人类带 3 可以形成对称和不对称的二聚体，具有不同的外向（OF）和内向（IF）状态的组合。这些结构还使我们能够获得第一个 IF 构象的人带 3 分子模型。基于这些二聚体的结构数据，我们提出了一种离子转运模型，该模型有利于电梯式机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/16cd6e420487/pbio.3002719.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/1d6a87b074cd/pbio.3002719.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/9f0bee83ce99/pbio.3002719.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/ad1fb12b5f3c/pbio.3002719.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/3628c50a05e2/pbio.3002719.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/ad43f1cb4b84/pbio.3002719.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/00b94992e0af/pbio.3002719.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/16cd6e420487/pbio.3002719.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/1d6a87b074cd/pbio.3002719.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/9f0bee83ce99/pbio.3002719.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/ad1fb12b5f3c/pbio.3002719.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/3628c50a05e2/pbio.3002719.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/ad43f1cb4b84/pbio.3002719.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/00b94992e0af/pbio.3002719.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2376/11338459/16cd6e420487/pbio.3002719.g007.jpg

相似文献

1
Cryo-EM structures of the human band 3 transporter indicate a transport mechanism involving the coupled movement of chloride and bicarbonate ions.冷冻电镜结构的人带 3 转运蛋白表明涉及耦合运动的氯离子和碳酸氢根离子的运输机制。
PLoS Biol. 2024 Aug 21;22(8):e3002719. doi: 10.1371/journal.pbio.3002719. eCollection 2024 Aug.
2
Molecular Insights into the Effect of Cholesterol on the Binding of Bicarbonate Ions in Band 3 Protein.胆固醇对带 3 蛋白结合碳酸氢根离子的影响的分子见解。
Langmuir. 2024 May 28;40(21):10908-10915. doi: 10.1021/acs.langmuir.4c00216. Epub 2024 May 13.
3
The carboxyl side chain of glutamate 681 interacts with a chloride binding modifier site that allosterically modulates the dimeric conformational state of band 3 (AE1). Implications for the mechanism of anion/proton cotransport.谷氨酸681的羧基侧链与一个氯离子结合调节位点相互作用，该位点通过变构调节带3（AE1）的二聚体构象状态。对阴离子/质子协同转运机制的启示。
Biochemistry. 2003 Feb 18;42(6):1589-602. doi: 10.1021/bi0205294.
4
CryoEM structures of anion exchanger 1 capture multiple states of inward- and outward-facing conformations.阴离子交换蛋白 1 的冷冻电镜结构捕获了内向和外向构象的多种状态。
Commun Biol. 2022 Dec 14;5(1):1372. doi: 10.1038/s42003-022-04306-8.
5
Asymmetry of inverted-topology repeats in the AE1 anion exchanger suggests an elevator-like mechanism.AE1 阴离子交换器中倒位拓扑重复的不对称性提示了一种类似于电梯的机制。
J Gen Physiol. 2017 Dec 4;149(12):1149-1164. doi: 10.1085/jgp.201711836. Epub 2017 Nov 22.
6
Cell physiology and molecular mechanism of anion transport by erythrocyte band 3/AE1.红细胞带 3/AE1 转运阴离子的细胞生理学和分子机制。
Am J Physiol Cell Physiol. 2021 Dec 1;321(6):C1028-C1059. doi: 10.1152/ajpcell.00275.2021. Epub 2021 Oct 20.
7
Evidence that anion transport by band 3 proceeds via a ping-pong mechanism involving a single transport site. A 35 Cl NMR study.有证据表明，带3蛋白介导的阴离子转运通过涉及单一转运位点的乒乓机制进行。一项³⁵Cl核磁共振研究。
J Biol Chem. 1985 Aug 15;260(17):9537-44.
8
Rapid Cl⁻/HCO⁻₃exchange kinetics of AE1 in HEK293 cells and hereditary stomatocytosis red blood cells.HEK293 细胞和遗传性口形红细胞增多症红细胞中 AE1 的快速 Cl⁻/HCO₃⁻₃交换动力学。
Am J Physiol Cell Physiol. 2013 Sep 15;305(6):C654-62. doi: 10.1152/ajpcell.00142.2013. Epub 2013 Jul 10.
9
Structure of the SLC4 transporter Bor1p in an inward-facing conformation.内向构象的SLC4转运蛋白Bor1p的结构。
Protein Sci. 2017 Jan;26(1):130-145. doi: 10.1002/pro.3061. Epub 2016 Oct 21.
10
Structural and functional properties of the transporter SLC26A6 reveal mechanism of coupled anion exchange.SLC26A6 转运蛋白的结构和功能特性揭示了偶联阴离子交换的机制。
Elife. 2023 Jun 23;12:RP87178. doi: 10.7554/eLife.87178.

引用本文的文献

1
Nanodiscs remain indispensable for Cryo-EM studies of membrane proteins.纳米盘对于膜蛋白的冷冻电镜研究仍然不可或缺。
Curr Opin Struct Biol. 2025 Jun;92:103042. doi: 10.1016/j.sbi.2025.103042. Epub 2025 Apr 8.

本文引用的文献

1
CryoEM structures of anion exchanger 1 capture multiple states of inward- and outward-facing conformations.阴离子交换蛋白 1 的冷冻电镜结构捕获了内向和外向构象的多种状态。
Commun Biol. 2022 Dec 14;5(1):1372. doi: 10.1038/s42003-022-04306-8.
2
Architecture of the human erythrocyte ankyrin-1 complex.人类红细胞锚蛋白-1 复合物的结构。
Nat Struct Mol Biol. 2022 Jul;29(7):706-718. doi: 10.1038/s41594-022-00792-w. Epub 2022 Jul 14.
3
Cell physiology and molecular mechanism of anion transport by erythrocyte band 3/AE1.红细胞带 3/AE1 转运阴离子的细胞生理学和分子机制。
Am J Physiol Cell Physiol. 2021 Dec 1;321(6):C1028-C1059. doi: 10.1152/ajpcell.00275.2021. Epub 2021 Oct 20.
4
A 'Build and Retrieve' methodology to simultaneously solve cryo-EM structures of membrane proteins.一种“构建与提取”的方法，可同时解析膜蛋白的冷冻电镜结构。
Nat Methods. 2021 Jan;18(1):69-75. doi: 10.1038/s41592-020-01021-2. Epub 2021 Jan 6.
5
Elevator-type mechanisms of membrane transport.膜转运的电梯式机制。
Biochem Soc Trans. 2020 Jun 30;48(3):1227-1241. doi: 10.1042/BST20200290.
6
Census of halide-binding sites in protein structures.蛋白质结构中卤化物结合位点的普查。
Bioinformatics. 2020 May 1;36(10):3064-3071. doi: 10.1093/bioinformatics/btaa079.
7
Structure of the human ClC-1 chloride channel.人 ClC-1 氯离子通道的结构。
PLoS Biol. 2019 Apr 25;17(4):e3000218. doi: 10.1371/journal.pbio.3000218. eCollection 2019 Apr.
8
Band 3 function and dysfunction in a structural context.带 3 结构的功能和失能。
Curr Opin Hematol. 2018 May;25(3):163-170. doi: 10.1097/MOH.0000000000000418.
9
Asymmetry of inverted-topology repeats in the AE1 anion exchanger suggests an elevator-like mechanism.AE1 阴离子交换器中倒位拓扑重复的不对称性提示了一种类似于电梯的机制。
J Gen Physiol. 2017 Dec 4;149(12):1149-1164. doi: 10.1085/jgp.201711836. Epub 2017 Nov 22.
10
cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination.cryoSPARC：用于快速无监督低温电子显微镜结构测定的算法。
Nat Methods. 2017 Mar;14(3):290-296. doi: 10.1038/nmeth.4169. Epub 2017 Feb 6.