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Title: Illuminating structural proteins in viral "dark matter" with metaproteomics

Abstract

Viruses are ecologically important, yet environmental virology is limited by dominance of unannotated genomic sequences representing taxonomic and functional "viral dark matter." Although recent analytical advances are rapidly improving taxonomic annotations, identifying functional darkmatter remains problematic. Here, we apply paired metaproteomics and dsDNA-targeted metagenomics to identify 1,875 virion-associated proteins from the ocean. Over one-half of these proteins were newly functionally annotated and represent abundant and widespread viral metagenome-derived protein clusters (PCs). One primarily unannotated PC dominated the dataset, but structural modeling and genomic context identified this PC as a previously unidentified capsid protein from multiple uncultivated tailed virus families. Furthermore, four of the five most abundant PCs in the metaproteome represent capsid proteins containing the HK97-like protein fold previously found in many viruses that infect all three domains of life. The dominance of these proteins within our dataset, as well as their global distribution throughout the world's oceans and seas, supports prior hypotheses that this HK97-like protein fold is the most abundant biological structure on Earth. Altogether, these culture-independent analyses improve virion-associated protein annotations, facilitate the investigation of proteins within natural viral communities, and offer a high-throughput means of illuminating functional viral dark matter.

Authors:
 [1];  [2];  [3];  [1];  [4];  [1];  [5];  [1];  [1]
  1. Univ. of Arizona, Tucson, AZ (United States); The Ohio State Univ., Columbus, OH (United States)
  2. Univ. of Arizona, Tucson, AZ (United States); Univ. of Southern California, Los Angeles, CA (United States)
  3. Univ. of Arizona, Tucson, AZ (United States); Roche Tissue Diagnostics, Oro Valley, AZ (United States)
  4. Univ. of Arizona, Tucson, AZ (United States); Cold Regions Research and Engineering Lab., Hanover, NH (United States)
  5. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Texas, El Paso, TX (United States)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE; Work for Others (WFO)
OSTI Identifier:
1287026
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 113; Journal Issue: 9; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; viruses; marine; proteins

Citation Formats

Brum, Jennifer R., Ignacio-Espinoza, J. Cesar, Kim, Eun -Hae, Trubl, Gareth, Jones, Robert M., Roux, Simon, Verberkmoes, Nathan C., Rich, Virginia I., and Sullivan, Matthew B. Illuminating structural proteins in viral "dark matter" with metaproteomics. United States: N. p., 2016. Web. doi:10.1073/pnas.1525139113.
Brum, Jennifer R., Ignacio-Espinoza, J. Cesar, Kim, Eun -Hae, Trubl, Gareth, Jones, Robert M., Roux, Simon, Verberkmoes, Nathan C., Rich, Virginia I., & Sullivan, Matthew B. Illuminating structural proteins in viral "dark matter" with metaproteomics. United States. doi:10.1073/pnas.1525139113.
Brum, Jennifer R., Ignacio-Espinoza, J. Cesar, Kim, Eun -Hae, Trubl, Gareth, Jones, Robert M., Roux, Simon, Verberkmoes, Nathan C., Rich, Virginia I., and Sullivan, Matthew B. Tue . "Illuminating structural proteins in viral "dark matter" with metaproteomics". United States. doi:10.1073/pnas.1525139113. https://www.osti.gov/servlets/purl/1287026.
@article{osti_1287026,
title = {Illuminating structural proteins in viral "dark matter" with metaproteomics},
author = {Brum, Jennifer R. and Ignacio-Espinoza, J. Cesar and Kim, Eun -Hae and Trubl, Gareth and Jones, Robert M. and Roux, Simon and Verberkmoes, Nathan C. and Rich, Virginia I. and Sullivan, Matthew B.},
abstractNote = {Viruses are ecologically important, yet environmental virology is limited by dominance of unannotated genomic sequences representing taxonomic and functional "viral dark matter." Although recent analytical advances are rapidly improving taxonomic annotations, identifying functional darkmatter remains problematic. Here, we apply paired metaproteomics and dsDNA-targeted metagenomics to identify 1,875 virion-associated proteins from the ocean. Over one-half of these proteins were newly functionally annotated and represent abundant and widespread viral metagenome-derived protein clusters (PCs). One primarily unannotated PC dominated the dataset, but structural modeling and genomic context identified this PC as a previously unidentified capsid protein from multiple uncultivated tailed virus families. Furthermore, four of the five most abundant PCs in the metaproteome represent capsid proteins containing the HK97-like protein fold previously found in many viruses that infect all three domains of life. The dominance of these proteins within our dataset, as well as their global distribution throughout the world's oceans and seas, supports prior hypotheses that this HK97-like protein fold is the most abundant biological structure on Earth. Altogether, these culture-independent analyses improve virion-associated protein annotations, facilitate the investigation of proteins within natural viral communities, and offer a high-throughput means of illuminating functional viral dark matter.},
doi = {10.1073/pnas.1525139113},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 9,
volume = 113,
place = {United States},
year = {2016},
month = {2}
}

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