On the emergence of P-Loop NTPase and Rossmann enzymes from a Beta-Alpha-Beta ancestral fragment

  1. Liam M Longo
  2. Jagoda Jabłońska
  3. Pratik Vyas
  4. Manil Kanade
  5. Rachel Kolodny
  6. Nir Ben-Tal
  7. Dan S Tawfik  Is a corresponding author
  1. Tokyo Institute of Technology, Japan
  2. Weizmann Institute of Science, Israel
  3. University of Haifa, Israel
  4. Tel Aviv University, Israel

Abstract

Dating back to the last universal common ancestor (LUCA), the P-loop NTPases and Rossmanns now comprise the most ubiquitous and diverse enzyme lineages. Intriguing similarities in their overall architecture and phosphate binding motifs suggest common ancestry; however, due to a lack of sequence identity and some fundamental structural differences, these families are considered independent emergences. To address this longstanding dichotomy, we systematically searched for 'bridge proteins' with structure and sequence elements shared by both lineages. We detected homologous segments that span the first βαβ segment of both lineages and include two key functional motifs: (i) a phosphate binding loop – the 'Walker A' motif of P-loop NTPases or the Rossmann equivalent, both residing at the N-terminus of α1; and (ii) an Asp at the tip of β2. The latter comprises the 'Walker B' aspartate that chelates the catalytic metal in P-loop NTPases, or the canonical Rossmann β2-Asp that binds the cofactor's ribose moiety. Tubulin, a Rossmann GTPase, demonstrates the potential of the β2-Asp to take either one of these two roles. We conclude that common P-loops/Rossmann ancestry is plausible, although convergence cannot be completely ruled out. Regardless, both lineages most likely emerged from a polypeptide comprising a βαβ segment carrying the above two functional motifs, a segment that comprises the core of both enzyme families to this very day.

Data availability

All data analysed in this manuscript are from publicly available archives such as the Protein Databank.

Article and author information

Author details

  1. Liam M Longo

    Earth-Life Science Institute, Tokyo Institute of Technology, Ookayama, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  2. Jagoda Jabłońska

    Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Pratik Vyas

    Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8961-5575
  4. Manil Kanade

    Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0076-8584
  5. Rachel Kolodny

    Department of Computer Science, University of Haifa, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Nir Ben-Tal

    Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6901-832X
  7. Dan S Tawfik

    Biomolecular Science, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    dan.tawfik@weizmann.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5914-8240

Funding

Volkswagen Foundation (94747)

  • Rachel Kolodny

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

Reviewing Editor

  1. Charlotte M Deane, University of Oxford, United Kingdom

Version history

  1. Received: October 31, 2020
  2. Accepted: December 4, 2020
  3. Accepted Manuscript published: December 9, 2020 (version 1)
  4. Version of Record published: December 23, 2020 (version 2)

Copyright

© 2020, Longo 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. Liam M Longo
  2. Jagoda Jabłońska
  3. Pratik Vyas
  4. Manil Kanade
  5. Rachel Kolodny
  6. Nir Ben-Tal
  7. Dan S Tawfik
(2020)
On the emergence of P-Loop NTPase and Rossmann enzymes from a Beta-Alpha-Beta ancestral fragment
eLife 9:e64415.
https://doi.org/10.7554/eLife.64415

Share this article

https://doi.org/10.7554/eLife.64415

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