Cryo-EM structure of the yeast TREX complex and coordination with the SR-like protein Gbp2

  1. Yihu Xie  Is a corresponding author
  2. Bradley P Clarke
  3. Yong Joon Kim
  4. Austin L Ivey
  5. Pate S Hill
  6. Yi Shi
  7. Yi Ren  Is a corresponding author
  1. Vanderbilt University, United States
  2. University of Pittsburgh, United States
  3. University of Pittsburgh School of Medicine, United States

Abstract

The evolutionarily conserved TREX complex plays central roles during mRNP (messenger ribonucleoprotein) maturation and export from the nucleus to the cytoplasm. In yeast, TREX is composed of the THO sub-complex (Tho2, Hpr1, Tex1, Mft1, and Thp2), the DEAD box ATPase Sub2, and Yra1. Here we present a 3.7 Å cryo-EM structure of the yeast THO•Sub2 complex. The structure reveals the intimate assembly of THO revolving around its largest subunit Tho2. THO stabilizes a semi-open conformation of the Sub2 ATPase via interactions with Tho2. We show that THO interacts with the SR-like protein Gbp2 through both the RS domain and RRM domains of Gbp2. Crosslinking mass spectrometry analysis supports the extensive interactions between THO and Gbp2, further revealing that RRM domains of Gbp2 are in close proximity to the C-terminal domain of Tho2. We propose that THO serves as a landing pad to configure Gbp2 to facilitate its loading onto mRNP.

Data availability

The cryo-EM density maps have been deposited in the Electron Microscopy Data Bank under the accession number EMD-23527. The coordinates of the THO•Sub2 complex has be deposited in the Protein Data Bank under the accession number 7LUV.

The following data sets were generated

Article and author information

Author details

  1. Yihu Xie

    Department of Biochemistry, Vanderbilt University, Nashville, United States
    For correspondence
    yihu.xie@vanderbilt.edu
    Competing interests
    The authors declare that no competing interests exist.
  2. Bradley P Clarke

    Department of Biochemistry, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9413-9905
  3. Yong Joon Kim

    Department of Cell Biology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Austin L Ivey

    Department of Biochemistry, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Pate S Hill

    Department of Biochemistry, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9550-2713
  6. Yi Shi

    Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2761-8324
  7. Yi Ren

    Department of Biochemistry, Vanderbilt University, Nashville, United States
    For correspondence
    yi.ren@vanderbilt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4531-0910

Funding

National Institute of General Medical Sciences (GM133743)

  • Yihu Xie
  • Bradley P Clarke
  • Austin L Ivey
  • Pate S Hill
  • Yi Ren

National Institute of General Medical Sciences (GM137905)

  • Yong Joon Kim
  • Yi Shi

National Cancer Institute (T32CA119925)

  • Bradley P Clarke

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Karsten Weis, ETH Zurich, Switzerland

Publication history

  1. Received: December 12, 2020
  2. Accepted: March 30, 2021
  3. Accepted Manuscript published: March 31, 2021 (version 1)
  4. Version of Record published: April 13, 2021 (version 2)

Copyright

© 2021, Xie et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Yihu Xie
  2. Bradley P Clarke
  3. Yong Joon Kim
  4. Austin L Ivey
  5. Pate S Hill
  6. Yi Shi
  7. Yi Ren
(2021)
Cryo-EM structure of the yeast TREX complex and coordination with the SR-like protein Gbp2
eLife 10:e65699.
https://doi.org/10.7554/eLife.65699
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