Robust and accurate prediction of residue-residue interactions across protein interfaces using evolutionary information

  1. Sergey Ovchinnikov
  2. Hetunandan Kamisetty
  3. David Baker  Is a corresponding author
  1. Howard Hughes Medical Institute, University of Washington, United States

Abstract

Do the amino acid sequence identities of residues that make contact across protein interfaces covary during evolution? If so, such covariance could be used to predict contacts across interfaces and assemble models of biological complexes. We find that residue pairs identified using a pseudo-likelihood based method to covary across protein-protein interfaces in the 50S ribosomal unit and 28 additional bacterial protein complexes with known structure are almost always in contact in the complex provided that the number of aligned sequences is greater than the average of the lengths of the two proteins. We use this method to make subunit contact predictions for an additional 36 protein complexes with unknown structures, and present models based on these predictions for the tripartite ATP-independent periplasmic (TRAP) transporter, the tripartite efflux system, the pyruvate formate lyase-activating enzyme complex, and the methionine ABC transporter.

Article and author information

Author details

  1. Sergey Ovchinnikov

    Howard Hughes Medical Institute, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Hetunandan Kamisetty

    Howard Hughes Medical Institute, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. David Baker

    Howard Hughes Medical Institute, University of Washington, Seattle, United States
    For correspondence
    dabaker@u.washington.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Benoit Roux, University of Chicago, United States

Version history

  1. Received: December 8, 2013
  2. Accepted: April 22, 2014
  3. Accepted Manuscript published: May 1, 2014 (version 1)
  4. Version of Record published: May 27, 2014 (version 2)

Copyright

© 2014, Ovchinnikov et al.

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

Metrics

  • 14,823
    views
  • 2,454
    downloads
  • 544
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Sergey Ovchinnikov
  2. Hetunandan Kamisetty
  3. David Baker
(2014)
Robust and accurate prediction of residue-residue interactions across protein interfaces using evolutionary information
eLife 3:e02030.
https://doi.org/10.7554/eLife.02030

Share this article

https://doi.org/10.7554/eLife.02030

Further reading

    1. Evolutionary Biology
    Case Vincent Miller, Jen A Bright ... Michael Pittman
    Research Article

    Enantiornithines were the dominant birds of the Mesozoic, but understanding of their diet is still tenuous. We introduce new data on the enantiornithine family Bohaiornithidae, famous for their large size and powerfully built teeth and claws. In tandem with previously published data, we comment on the breadth of enantiornithine ecology and potential patterns in which it evolved. Body mass, jaw mechanical advantage, finite element analysis of the jaw, and traditional morphometrics of the claws and skull are compared between bohaiornithids and living birds. We find bohaiornithids to be more ecologically diverse than any other enantiornithine family: Bohaiornis and Parabohaiornis are similar to living plant-eating birds; Longusunguis resembles raptorial carnivores; Zhouornis is similar to both fruit-eating birds and generalist feeders; and Shenqiornis and Sulcavis plausibly ate fish, plants, or a mix of both. We predict the ancestral enantiornithine bird to have been a generalist which ate a wide variety of foods. However, more quantitative data from across the enantiornithine tree is needed to refine this prediction. By the Early Cretaceous, enantiornithine birds had diversified into a variety of ecological niches like crown birds after the K-Pg extinction, adding to the evidence that traits unique to crown birds cannot completely explain their ecological success.

    1. Evolutionary Biology
    Mátyás Paczkó, Eörs Szathmáry, András Szilágyi
    Research Article

    The RNA world hypothesis proposes that during the early evolution of life, primordial genomes of the first self-propagating evolutionary units existed in the form of RNA-like polymers. Autonomous, non-enzymatic, and sustained replication of such information carriers presents a problem, because product formation and hybridization between template and copy strands reduces replication speed. Kinetics of growth is then parabolic with the benefit of entailing competitive coexistence, thereby maintaining diversity. Here, we test the information-maintaining ability of parabolic growth in stochastic multispecies population models under the constraints of constant total population size and chemostat conditions. We find that large population sizes and small differences in the replication rates favor the stable coexistence of the vast majority of replicator species (‘genes’), while the error threshold problem is alleviated relative to exponential amplification. In addition, sequence properties (GC content) and the strength of resource competition mediated by the rate of resource inflow determine the number of coexisting variants, suggesting that fluctuations in building block availability favored repeated cycles of exploration and exploitation. Stochastic parabolic growth could thus have played a pivotal role in preserving viable sequences generated by random abiotic synthesis and providing diverse genetic raw material to the early evolution of functional ribozymes.