IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-54147-8.html
   My bibliography  Save this article

Structure of a dimeric full-length ABC transporter

Author

Listed:
  • Sarah C. Bickers

    (University of Toronto
    University of Toronto Mississauga)

  • Samir Benlekbir

    (The Hospital for Sick Children)

  • John L. Rubinstein

    (The Hospital for Sick Children
    University of Toronto
    University of Toronto)

  • Voula Kanelis

    (University of Toronto
    University of Toronto Mississauga
    University of Toronto
    The Hospital for Sick Children)

Abstract

Activities of ATP binding cassette (ABC) proteins are regulated by multiple mechanisms, including protein interactions, phosphorylation, proteolytic processing, and/or oligomerization of the ABC protein itself. Here we present the structure of yeast cadmium factor 1 (Ycf1p) in its mature form following cleavage by Pep4p protease. Ycf1p, a C subfamily ABC protein (ABCC), is homologue of human multidrug resistance protein 1. Remarkably, a portion of cleaved Ycf1p forms a well-ordered dimer, alongside monomeric particles also present in solution. While numerous other ABC proteins have been proposed to dimerize, no high-resolution structures have been reported. Both phosphorylation of the regulatory (R) region and ATPase activity are lower in the Ycf1p dimer compared to the monomer, indicating that dimerization affects Ycf1p function. The interface between Ycf1p protomers features protein-protein interactions and contains bound lipids, suggesting that lipids stabilize the dimer. The Ycf1p dimer structure may inform the dimerization interfaces of other ABCC dimers.

Suggested Citation

  • Sarah C. Bickers & Samir Benlekbir & John L. Rubinstein & Voula Kanelis, 2024. "Structure of a dimeric full-length ABC transporter," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54147-8
    DOI: 10.1038/s41467-024-54147-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-54147-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-54147-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Nitesh Kumar Khandelwal & Cinthia R. Millan & Samantha I. Zangari & Samantha Avila & Dewight Williams & Tarjani M. Thaker & Thomas M. Tomasiak, 2022. "The structural basis for regulation of the glutathione transporter Ycf1 by regulatory domain phosphorylation," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Michael L. Oldham & Richard K. Hite & Alanna M. Steffen & Ermelinda Damko & Zongli Li & Thomas Walz & Jue Chen, 2016. "A mechanism of viral immune evasion revealed by cryo-EM analysis of the TAP transporter," Nature, Nature, vol. 529(7587), pages 537-540, January.
    3. Andreas Blees & Dovile Januliene & Tommy Hofmann & Nicole Koller & Carla Schmidt & Simon Trowitzsch & Arne Moeller & Robert Tampé, 2017. "Structure of the human MHC-I peptide-loading complex," Nature, Nature, vol. 551(7681), pages 525-528, November.
    4. Kallol Gupta & Joseph A. C. Donlan & Jonathan T. S. Hopper & Povilas Uzdavinys & Michael Landreh & Weston B. Struwe & David Drew & Andrew J. Baldwin & Phillip J. Stansfeld & Carol V. Robinson, 2017. "The role of interfacial lipids in stabilizing membrane protein oligomers," Nature, Nature, vol. 541(7637), pages 421-424, January.
    5. Jun Gyou Park & Songwon Kim & Eunhong Jang & Seung Hun Choi & Hyunsu Han & Seulgi Ju & Ji Won Kim & Da Sol Min & Mi Sun Jin, 2022. "The lysosomal transporter TAPL has a dual role as peptide translocator and phosphatidylserine floppase," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Nitesh Kumar Khandelwal & Thomas M. Tomasiak, 2024. "Structural basis for autoinhibition by the dephosphorylated regulatory domain of Ycf1," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Nitesh Kumar Khandelwal & Thomas M. Tomasiak, 2024. "Structural basis for autoinhibition by the dephosphorylated regulatory domain of Ycf1," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Ying Huang & Chenyang Xue & Ruiqian Bu & Cang Wu & Jiachen Li & Jinqiu Zhang & Jinyu Chen & Zhaoying Shi & Yonglong Chen & Yong Wang & Zhongmin Liu, 2024. "Inhibition and transport mechanisms of the ABC transporter hMRP5," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Yao-Xu Mao & Zhi-Peng Chen & Liang Wang & Jie Wang & Cong-Zhao Zhou & Wen-Tao Hou & Yuxing Chen, 2024. "Transport mechanism of human bilirubin transporter ABCC2 tuned by the inter-module regulatory domain," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    4. Vishal Maingi & Zhao Zhang & Chris Thachuk & Namita Sarraf & Edwin R. Chapman & Paul W. K. Rothemund, 2023. "Digital nanoreactors to control absolute stoichiometry and spatiotemporal behavior of DNA receptors within lipid bilayers," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Jixing Lyu & Chang Liu & Tianqi Zhang & Samantha Schrecke & Nicklaus P. Elam & Charles Packianathan & Georg K. A. Hochberg & David Russell & Minglei Zhao & Arthur Laganowsky, 2022. "Structural basis for lipid and copper regulation of the ABC transporter MsbA," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    6. Tiziano Mazza & Theodoros I. Roumeliotis & Elena Garitta & David Drew & S. Tamir Rashid & Cesare Indiveri & Jyoti S. Choudhary & Kenneth J. Linton & Konstantinos Beis, 2024. "Structural basis for the modulation of MRP2 activity by phosphorylation and drugs," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Dian Ding & Tianyi Hou & Miao Wei & Jing-Xiang Wu & Lei Chen, 2023. "The inhibition mechanism of the SUR2A-containing KATP channel by a regulatory helix," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. Takaaki A. Kobayashi & Hiroto Shimada & Fumiya K. Sano & Yuzuru Itoh & Sawako Enoki & Yasushi Okada & Tsukasa Kusakizako & Osamu Nureki, 2024. "Dimeric transport mechanism of human vitamin C transporter SVCT1," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    9. Jiansheng Jiang & Daniel K. Taylor & Ellen J. Kim & Lisa F. Boyd & Javeed Ahmad & Michael G. Mage & Hau V. Truong & Claire H. Woodward & Nikolaos G. Sgourakis & Peter Cresswell & David H. Margulies & , 2022. "Structural mechanism of tapasin-mediated MHC-I peptide loading in antigen presentation," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    10. Yongchan Lee & Pattama Wiriyasermkul & Pornparn Kongpracha & Satomi Moriyama & Deryck J. Mills & Werner Kühlbrandt & Shushi Nagamori, 2022. "Ca2+-mediated higher-order assembly of heterodimers in amino acid transport system b0,+ biogenesis and cystinuria," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    11. Alexander Domnick & Christian Winter & Lukas Sušac & Leon Hennecke & Mario Hensen & Nicole Zitzmann & Simon Trowitzsch & Christoph Thomas & Robert Tampé, 2022. "Molecular basis of MHC I quality control in the peptide loading complex," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    12. Lenong Li & Xubiao Peng & Mansoor Batliwala & Marlene Bouvier, 2023. "Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    13. Xin Lei & Indu Khatri & Tom Wit & Iris Rink & Marja Nieuwland & Ron Kerkhoven & Hans Eenennaam & Chong Sun & Abhishek D. Garg & Jannie Borst & Yanling Xiao, 2023. "CD4+ helper T cells endow cDC1 with cancer-impeding functions in the human tumor micro-environment," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    14. Junke Liu & Hengmin Tang & Chanjuan Xu & Shengnan Zhou & Xunying Zhu & Yuanyuan Li & Laurent Prézeau & Tao Xu & Jean-Philippe Pin & Philippe Rondard & Wei Ji & Jianfeng Liu, 2022. "Biased signaling due to oligomerization of the G protein-coupled platelet-activating factor receptor," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    15. Yongxiang Zhao & Heidi Schubert & Alan Blakely & Biff Forbush & Micholas Dean Smith & Jesse Rinehart & Erhu Cao, 2024. "Structural bases for Na+-Cl− cotransporter inhibition by thiazide diuretic drugs and activation by kinases," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    16. Ines Katharina Müller & Christian Winter & Christoph Thomas & Robbert M. Spaapen & Simon Trowitzsch & Robert Tampé, 2022. "Structure of an MHC I–tapasin–ERp57 editing complex defines chaperone promiscuity," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    17. Di Wu & Renhong Yan & Siyuan Song & Andrew K. Swansiger & Yaning Li & James S. Prell & Qiang Zhou & Carol V. Robinson, 2024. "The complete assembly of human LAT1-4F2hc complex provides insights into its regulation, function and localisation," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    18. Jun Gyou Park & Songwon Kim & Eunhong Jang & Seung Hun Choi & Hyunsu Han & Seulgi Ju & Ji Won Kim & Da Sol Min & Mi Sun Jin, 2022. "The lysosomal transporter TAPL has a dual role as peptide translocator and phosphatidylserine floppase," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    19. Tianqi Zhang & Jixing Lyu & Bowei Yang & Sangho D. Yun & Elena Scott & Minglei Zhao & Arthur Laganowsky, 2024. "Native mass spectrometry and structural studies reveal modulation of MsbA–nucleotide interactions by lipids," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    20. Abraham O. Oluwole & Robin A. Corey & Chelsea M. Brown & Victor M. Hernández-Rocamora & Phillip J. Stansfeld & Waldemar Vollmer & Jani R. Bolla & Carol V. Robinson, 2022. "Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54147-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.