Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 52, Pages 15898-15903Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1508380112
Keywords
structure prediction; protein disorder; transmembrane proteins; secreted proteins; unknown unknowns
Categories
Funding
- Commonwealth Scientific and Industrial Research Organisation's Office of the Chief Executive Science Leader program and Computational and Simulation Sciences platform
- Alexander von Humboldt Foundation
- Fundacao para a Ciencia e Tecnologia
Ask authors/readers for more resources
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 similar to 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available