Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

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Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases. / Boomsma, Wouter Krogh; Nielsen, Sofie Vincents; Lindorff-Larsen, Kresten; Hartmann-Petersen, Rasmus; Ellgaard, Lars.

I: PeerJ, Bind 4, e1725, 2016.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Boomsma, WK, Nielsen, SV, Lindorff-Larsen, K, Hartmann-Petersen, R & Ellgaard, L 2016, 'Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases', PeerJ, bind 4, e1725. https://doi.org/10.7717/peerj.1725

APA

Boomsma, W. K., Nielsen, S. V., Lindorff-Larsen, K., Hartmann-Petersen, R., & Ellgaard, L. (2016). Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases. PeerJ, 4, [e1725]. https://doi.org/10.7717/peerj.1725

Vancouver

Boomsma WK, Nielsen SV, Lindorff-Larsen K, Hartmann-Petersen R, Ellgaard L. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases. PeerJ. 2016;4. e1725. https://doi.org/10.7717/peerj.1725

Author

Boomsma, Wouter Krogh ; Nielsen, Sofie Vincents ; Lindorff-Larsen, Kresten ; Hartmann-Petersen, Rasmus ; Ellgaard, Lars. / Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases. I: PeerJ. 2016 ; Bind 4.

Bibtex

@article{e262be936c4d47f4beb15b9d4519378b,
title = "Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases",
abstract = "The ubiquitin-proteasome system targets misfolded proteins for degradation. Since the accumulation of such proteins is potentially harmful for the cell, their prompt removal is important. E3 ubiquitin-protein ligases mediate substrate ubiquitination by bringing together the substrate with an E2 ubiquitin-conjugating enzyme, which transfers ubiquitin to the substrate. For misfolded proteins, substrate recognition is generally delegated to molecular chaperones that subsequently interact with specific E3 ligases. An important exception is San1, a yeast E3 ligase. San1 harbors extensive regions of intrinsic disorder, which provide both conformational flexibility and sites for direct recognition of misfolded targets of vastly different conformations. So far, no mammalian ortholog of San1 is known, nor is it clear whether other E3 ligases utilize disordered regions for substrate recognition. Here, we conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology of their ordered regions, and did not capture the unique disorder patterns that encode the functional mechanism of San1. However, by searching specifically for key features of the San1 sequence, such as long regions of intrinsic disorder embedded with short stretches predicted to be suitable for substrate interaction, we identified several E3 ligases with these characteristics. Our initial analysis revealed that another remarkable trait of San1 is shared with several candidate E3 ligases: long stretches of complete lysine suppression, which in San1 limits auto-ubiquitination. We encode these characteristic features into a San1 similarity-score, and present a set of proteins that are plausible candidates as San1 counterparts in humans. In conclusion, our work indicates that San1 is not a unique case, and that several other yeast and human E3 ligases have sequence properties that may allow them to recognize substrates by a similar mechanism as San1.",
author = "Boomsma, {Wouter Krogh} and Nielsen, {Sofie Vincents} and Kresten Lindorff-Larsen and Rasmus Hartmann-Petersen and Lars Ellgaard",
year = "2016",
doi = "10.7717/peerj.1725",
language = "English",
volume = "4",
journal = "PeerJ",
issn = "2167-8359",
publisher = "PeerJ",

}

RIS

TY - JOUR

T1 - Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

AU - Boomsma, Wouter Krogh

AU - Nielsen, Sofie Vincents

AU - Lindorff-Larsen, Kresten

AU - Hartmann-Petersen, Rasmus

AU - Ellgaard, Lars

PY - 2016

Y1 - 2016

N2 - The ubiquitin-proteasome system targets misfolded proteins for degradation. Since the accumulation of such proteins is potentially harmful for the cell, their prompt removal is important. E3 ubiquitin-protein ligases mediate substrate ubiquitination by bringing together the substrate with an E2 ubiquitin-conjugating enzyme, which transfers ubiquitin to the substrate. For misfolded proteins, substrate recognition is generally delegated to molecular chaperones that subsequently interact with specific E3 ligases. An important exception is San1, a yeast E3 ligase. San1 harbors extensive regions of intrinsic disorder, which provide both conformational flexibility and sites for direct recognition of misfolded targets of vastly different conformations. So far, no mammalian ortholog of San1 is known, nor is it clear whether other E3 ligases utilize disordered regions for substrate recognition. Here, we conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology of their ordered regions, and did not capture the unique disorder patterns that encode the functional mechanism of San1. However, by searching specifically for key features of the San1 sequence, such as long regions of intrinsic disorder embedded with short stretches predicted to be suitable for substrate interaction, we identified several E3 ligases with these characteristics. Our initial analysis revealed that another remarkable trait of San1 is shared with several candidate E3 ligases: long stretches of complete lysine suppression, which in San1 limits auto-ubiquitination. We encode these characteristic features into a San1 similarity-score, and present a set of proteins that are plausible candidates as San1 counterparts in humans. In conclusion, our work indicates that San1 is not a unique case, and that several other yeast and human E3 ligases have sequence properties that may allow them to recognize substrates by a similar mechanism as San1.

AB - The ubiquitin-proteasome system targets misfolded proteins for degradation. Since the accumulation of such proteins is potentially harmful for the cell, their prompt removal is important. E3 ubiquitin-protein ligases mediate substrate ubiquitination by bringing together the substrate with an E2 ubiquitin-conjugating enzyme, which transfers ubiquitin to the substrate. For misfolded proteins, substrate recognition is generally delegated to molecular chaperones that subsequently interact with specific E3 ligases. An important exception is San1, a yeast E3 ligase. San1 harbors extensive regions of intrinsic disorder, which provide both conformational flexibility and sites for direct recognition of misfolded targets of vastly different conformations. So far, no mammalian ortholog of San1 is known, nor is it clear whether other E3 ligases utilize disordered regions for substrate recognition. Here, we conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology of their ordered regions, and did not capture the unique disorder patterns that encode the functional mechanism of San1. However, by searching specifically for key features of the San1 sequence, such as long regions of intrinsic disorder embedded with short stretches predicted to be suitable for substrate interaction, we identified several E3 ligases with these characteristics. Our initial analysis revealed that another remarkable trait of San1 is shared with several candidate E3 ligases: long stretches of complete lysine suppression, which in San1 limits auto-ubiquitination. We encode these characteristic features into a San1 similarity-score, and present a set of proteins that are plausible candidates as San1 counterparts in humans. In conclusion, our work indicates that San1 is not a unique case, and that several other yeast and human E3 ligases have sequence properties that may allow them to recognize substrates by a similar mechanism as San1.

U2 - 10.7717/peerj.1725

DO - 10.7717/peerj.1725

M3 - Journal article

C2 - 26966660

VL - 4

JO - PeerJ

JF - PeerJ

SN - 2167-8359

M1 - e1725

ER -

ID: 160125103