IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms13416.html
   My bibliography  Save this article

Functional competence of a partially engaged GPCR–β-arrestin complex

Author

Listed:
  • Punita Kumari

    (Indian Institute of Technology)

  • Ashish Srivastava

    (Indian Institute of Technology)

  • Ramanuj Banerjee

    (Indian Institute of Technology)

  • Eshan Ghosh

    (Indian Institute of Technology)

  • Pragya Gupta

    (Indian Institute of Technology)

  • Ravi Ranjan

    (Indian Institute of Technology)

  • Xin Chen

    (School of Pharmaceutical Engineering and Life Sciences, Changzhou University)

  • Bhagyashri Gupta

    (Indian Institute of Technology)

  • Charu Gupta

    (Indian Institute of Technology)

  • Deepika Jaiman

    (Indian Institute of Technology)

  • Arun K. Shukla

    (Indian Institute of Technology)

Abstract

G Protein-coupled receptors (GPCRs) constitute the largest family of cell surface receptors and drug targets. GPCR signalling and desensitization is critically regulated by β-arrestins (βarr). GPCR–βarr interaction is biphasic where the phosphorylated carboxyl terminus of GPCRs docks to the N-domain of βarr first and then seven transmembrane core of the receptor engages with βarr. It is currently unknown whether fully engaged GPCR–βarr complex is essential for functional outcomes or partially engaged complex can also be functionally competent. Here we assemble partially and fully engaged complexes of a chimeric β2V2R with βarr1, and discover that the core interaction is dispensable for receptor endocytosis, ERK MAP kinase binding and activation. Furthermore, we observe that carvedilol, a βarr biased ligand, does not promote detectable engagement between βarr1 and the receptor core. These findings uncover a previously unknown aspect of GPCR-βarr interaction and provide novel insights into GPCR signalling and regulatory paradigms.

Suggested Citation

  • Punita Kumari & Ashish Srivastava & Ramanuj Banerjee & Eshan Ghosh & Pragya Gupta & Ravi Ranjan & Xin Chen & Bhagyashri Gupta & Charu Gupta & Deepika Jaiman & Arun K. Shukla, 2016. "Functional competence of a partially engaged GPCR–β-arrestin complex," Nature Communications, Nature, vol. 7(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13416
    DOI: 10.1038/ncomms13416
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms13416
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms13416?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Mithu Baidya & Madhu Chaturvedi & Hemlata Dwivedi-Agnihotri & Ashutosh Ranjan & Dominic Devost & Yoon Namkung & Tomasz Maciej Stepniewski & Shubhi Pandey & Minakshi Baruah & Bhanupriya Panigrahi & Par, 2022. "Allosteric modulation of GPCR-induced β-arrestin trafficking and signaling by a synthetic intrabody," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Dylan Scott Eiger & Noelia Boldizsar & Christopher Cole Honeycutt & Julia Gardner & Stephen Kirchner & Chloe Hicks & Issac Choi & Uyen Pham & Kevin Zheng & Anmol Warman & Jeffrey S. Smith & Jennifer Y, 2022. "Location bias contributes to functionally selective responses of biased CXCR3 agonists," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Parishmita Sarma & Carlo Marion C. Carino & Deeksha Seetharama & Shubhi Pandey & Hemlata Dwivedi-Agnihotri & Xue Rui & Yubo Cao & Kouki Kawakami & Poonam Kumari & Yu-Chih Chen & Kathryn E. Luker & Pre, 2023. "Molecular insights into intrinsic transducer-coupling bias in the CXCR4-CXCR7 system," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Yutaro Shiraishi & Yutaka Kofuku & Takumi Ueda & Shubhi Pandey & Hemlata Dwivedi-Agnihotri & Arun K. Shukla & Ichio Shimada, 2021. "Biphasic activation of β-arrestin 1 upon interaction with a GPCR revealed by methyl-TROSY NMR," Nature Communications, Nature, vol. 12(1), pages 1-11, 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:7:y:2016:i:1:d:10.1038_ncomms13416. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.