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Title: Flexibility and Design: Conformational Heterogeneity along the Evolutionary Trajectory of a Redesigned Ubiquitin

Authors:
; ; ; ;
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1435654
Alternate Identifier(s):
OSTI ID: 1398563
Grant/Contract Number:
AC02-05CH11231; MR-15-32859
Resource Type:
Journal Article: Published Article
Journal Name:
Structure
Additional Journal Information:
Journal Volume: 25; Journal Issue: 5; Related Information: CHORUS Timestamp: 2018-05-01 21:16:27; Journal ID: ISSN 0969-2126
Publisher:
Elsevier
Country of Publication:
United Kingdom
Language:
English

Citation Formats

Biel, Justin T., Thompson, Michael C., Cunningham, Christian N., Corn, Jacob E., and Fraser, James S. Flexibility and Design: Conformational Heterogeneity along the Evolutionary Trajectory of a Redesigned Ubiquitin. United Kingdom: N. p., 2017. Web. doi:10.1016/j.str.2017.03.009.
Biel, Justin T., Thompson, Michael C., Cunningham, Christian N., Corn, Jacob E., & Fraser, James S. Flexibility and Design: Conformational Heterogeneity along the Evolutionary Trajectory of a Redesigned Ubiquitin. United Kingdom. doi:10.1016/j.str.2017.03.009.
Biel, Justin T., Thompson, Michael C., Cunningham, Christian N., Corn, Jacob E., and Fraser, James S. Mon . "Flexibility and Design: Conformational Heterogeneity along the Evolutionary Trajectory of a Redesigned Ubiquitin". United Kingdom. doi:10.1016/j.str.2017.03.009.
@article{osti_1435654,
title = {Flexibility and Design: Conformational Heterogeneity along the Evolutionary Trajectory of a Redesigned Ubiquitin},
author = {Biel, Justin T. and Thompson, Michael C. and Cunningham, Christian N. and Corn, Jacob E. and Fraser, James S.},
abstractNote = {},
doi = {10.1016/j.str.2017.03.009},
journal = {Structure},
number = 5,
volume = 25,
place = {United Kingdom},
year = {Mon May 01 00:00:00 EDT 2017},
month = {Mon May 01 00:00:00 EDT 2017}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1016/j.str.2017.03.009

Citation Metrics:
Cited by: 4works
Citation information provided by
Web of Science

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  • Cited by 4
  • No abstract prepared.
  • The Josephin domain is a conserved cysteine protease domain found in four human deubiquitinating enzymes: ataxin-3, the ataxin-3-like protein (ATXN3L), Josephin-1, and Josephin-2. Josephin domains from these four proteins were purified and assayed for their ability to cleave ubiquitin substrates. Reaction rates differed markedly both among the different proteins and for different substrates with a given protein. The ATXN3L Josephin domain is a significantly more efficient enzyme than the ataxin-3 domain despite their sharing 85% sequence identity. To understand the structural basis of this difference, the 2.6 {angstrom} x-ray crystal structure of the ATXN3L Josephin domain in complex with ubiquitinmore » was determined. Although ataxin-3 and ATXN3L adopt similar folds, they bind ubiquitin in different, overlapping sites. Mutations were made in ataxin-3 at selected positions, introducing the corresponding ATXN3L residue. Only three such mutations are sufficient to increase the catalytic activity of the ataxin-3 domain to levels comparable with that of ATXN3L, suggesting that ataxin-3 has been subject to evolutionary restraints that keep its deubiquitinating activity in check.« less
  • No abstract prepared.
  • A new crystal structure of human ubiquitin is reported at 1.8 {angstrom} resolution. Compared with the other known crystal structure or the solution NMR structure of monomeric human ubiquitin, this new structure is similar in its overall fold but differs with respect to the conformation of the backbone in a surface-exposed region. The conformation reported here resembles conformations previously seen in complex with deubiquinating enzymes, wherein the Asp52/Gly53 main chain and Glu24 side chain move. This movement exposes the backbone carbonyl of Asp52 to the exterior of the molecule, making it possible to engage in hydrogen-bond contacts with neighboring molecules,more » rather than in an internal hydrogen bond with the backbone of Glu24. This particular crystal form of ubiquitin has been used in a large number of solid state NMR studies. The structure described here elucidates the origin of many of the chemical shift differences comparing solution and solid state studies.« less