Unexpected features of the dark proteome
Nelson Perdigão a,b, Julian Heinrich c, Christian Stolte c, Kenneth S. Sabir d,e, Michael J. Buckley c, Bruce Tabor c, Beth Signal d, Brian S. Gloss d, Christopher J. Hammang d, Burkhard Rost f, Andrea Schafferhans f, and Seán I. O’Donoghue c,d,g,1
aInstituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal;
bInstituto de Sistemas e Robótica, 1049-001 Lisbon, Portugal;
cCommonwealth Scientific and Industrial Research Organisation (CSIRO), Sydney, NSW 1670, Australia;
dGenomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia;
eSchool of Information Technology, The University of Sydney, Sydney, NSW 2006, Australia;
fDepartment for Bioinformatics and Computational Biology, Technische Universität München, 80333 Munich, Germany;
gSchool of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia
Edited by Alan R. Fersht, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom, and approved October 13, 2015 (received for review April 29, 2015)
Significance
A key remaining frontier in our understanding of biological systems is the “dark proteome”—that is, the regions of proteins where molecular conformation is completely unknown. We systematically surveyed these regions, finding that nearly half of the proteome in eukaryotes is dark and that, surprisingly, most of the darkness cannot be accounted for. We also found that the dark proteome has unexpected features, including an association with secretory tissues, disulfide bonding, low evolutionary conservation, and very few known interactions with other proteins. This work will help future research shed light on the remaining dark proteome, thus revealing molecular processes of life that are currently unknown.
Abstract
We surveyed the “dark” proteome–that is, regions of proteins never observed by experimental structure determination and inaccessible to homology modeling. For 546,000 Swiss-Prot proteins, we found that 44–54% of the proteome in eukaryotes and viruses was dark, compared with only ∼14% in archaea and bacteria. Surprisingly, most of the dark proteome could not be accounted for by conventional explanations, such as intrinsic disorder or transmembrane regions. Nearly half of the dark proteome comprised dark proteins, in which the entire sequence lacked similarity to any known structure. Dark proteins fulfill a wide variety of functions, but a subset showed distinct and largely unexpected features, such as association with secretion, specific tissues, the endoplasmic reticulum, disulfide bonding, and proteolytic cleavage. Dark proteins also had short sequence length, low evolutionary reuse, and few known interactions with other proteins. These results suggest new research directions in structural and computational biology.
structure prediction protein disorder transmembrane proteins secreted proteins unknown unknowns
Footnotes
1To whom correspondence should be addressed. Email: sean{at}odonoghuelab.org.
Author contributions: S.I.O. designed research; N.P., J.H., K.S.S., M.J.B., B.T., B.S., B.S.G., C.J.H., and A.S. performed research; N.P., J.H., C.S., B.R., A.S., and S.I.O. analyzed data; and S.I.O. wrote the paper with contributions from N.P.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: This work is accompanied by an online resource (darkproteins.org) that provides periodically updated versions of Datasets S1 and S2, and provides facilities to interactively explore these data.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1508380112/-/DCSupplemental.
Freely available online through the PNAS open access option.
FREE PDF GRATIS: PNAS
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Mas Darwin já não tinha explicado tudo sobre o fato, Fato, FATO da evolução??? E agora tem isso de "dark proteome"? Pode isso, Arnaldo?
Este blogger foi evolucionista de carteirinha, mas deixou de apostar no pangaré de Darwin em 1998, e aposto desde então todas as suas fichas no Design Inteligente.
Darwin kaput! Viva Darwin!!!
Este blogger foi evolucionista de carteirinha, mas deixou de apostar no pangaré de Darwin em 1998, e aposto desde então todas as suas fichas no Design Inteligente.
Darwin kaput! Viva Darwin!!!
