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Title: System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes

Authors:
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  1. SJCH
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Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1247364
Resource Type:
Journal Article
Resource Relation:
Journal Name: Molecular Cell; Journal Volume: 62; Journal Issue: (1) ; 04, 2016
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Zhang, Wei, Wu, Kuen-Phon, Sartori, Maria A., Kamadurai, Hari B., Ordureau, Alban, Jiang, Chong, Mercredi, Peter Y., Murchie, Ryan, Hu, Jicheng, Persaud, Avinash, Mukherjee, Manjeet, Li, Nan, Doye, Anne, Walker, John R., Sheng, Yi, Hao, Zhenyue, Li, Yanjun, Brown, Kevin R., Lemichez, Emmanuel, Chen, Junjie, Tong, Yufeng, Harper, J. Wade, Moffat, Jason, Rotin, Daniela, Schulman, Brenda A., Sidhu, Sachdev S., Texas), Toronto), York), Harvard-Med), and UHN). System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes. United States: N. p., 2016. Web. doi:10.1016/j.molcel.2016.02.005.
Zhang, Wei, Wu, Kuen-Phon, Sartori, Maria A., Kamadurai, Hari B., Ordureau, Alban, Jiang, Chong, Mercredi, Peter Y., Murchie, Ryan, Hu, Jicheng, Persaud, Avinash, Mukherjee, Manjeet, Li, Nan, Doye, Anne, Walker, John R., Sheng, Yi, Hao, Zhenyue, Li, Yanjun, Brown, Kevin R., Lemichez, Emmanuel, Chen, Junjie, Tong, Yufeng, Harper, J. Wade, Moffat, Jason, Rotin, Daniela, Schulman, Brenda A., Sidhu, Sachdev S., Texas), Toronto), York), Harvard-Med), & UHN). System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes. United States. doi:10.1016/j.molcel.2016.02.005.
Zhang, Wei, Wu, Kuen-Phon, Sartori, Maria A., Kamadurai, Hari B., Ordureau, Alban, Jiang, Chong, Mercredi, Peter Y., Murchie, Ryan, Hu, Jicheng, Persaud, Avinash, Mukherjee, Manjeet, Li, Nan, Doye, Anne, Walker, John R., Sheng, Yi, Hao, Zhenyue, Li, Yanjun, Brown, Kevin R., Lemichez, Emmanuel, Chen, Junjie, Tong, Yufeng, Harper, J. Wade, Moffat, Jason, Rotin, Daniela, Schulman, Brenda A., Sidhu, Sachdev S., Texas), Toronto), York), Harvard-Med), and UHN). 2016. "System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes". United States. doi:10.1016/j.molcel.2016.02.005.
@article{osti_1247364,
title = {System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes},
author = {Zhang, Wei and Wu, Kuen-Phon and Sartori, Maria A. and Kamadurai, Hari B. and Ordureau, Alban and Jiang, Chong and Mercredi, Peter Y. and Murchie, Ryan and Hu, Jicheng and Persaud, Avinash and Mukherjee, Manjeet and Li, Nan and Doye, Anne and Walker, John R. and Sheng, Yi and Hao, Zhenyue and Li, Yanjun and Brown, Kevin R. and Lemichez, Emmanuel and Chen, Junjie and Tong, Yufeng and Harper, J. Wade and Moffat, Jason and Rotin, Daniela and Schulman, Brenda A. and Sidhu, Sachdev S. and Texas) and Toronto) and York) and Harvard-Med) and UHN)},
abstractNote = {},
doi = {10.1016/j.molcel.2016.02.005},
journal = {Molecular Cell},
number = (1) ; 04, 2016,
volume = 62,
place = {United States},
year = 2016,
month = 7
}
  • Cited by 14
  • Cited by 14
  • In eukaryotes, ubiquitination is an important posttranslational process achieved through a cascade of ubiquitin-activating (E1), conjugating (E2), and ligase (E3) enzymes. Many pathogenic bacteria deliver virulence factors into the host cell that function as E3 ligases. How these bacterial 'Trojan horses' integrate into the eukaryotic ubiquitin system has remained a mystery. Here we report crystal structures of two bacterial E3s, Salmonella SopA and Escherichia coli NleL, both in complex with human E2 UbcH7. These structures represent two distinct conformational states of the bacterial E3s, supporting the necessary structural rearrangements associated with ubiquitin transfer. The E2-interacting surface of SopA and NleLmore » has little similarity to those of eukaryotic E3s. However, both bacterial E3s bind to the canonical surface of E2 that normally interacts with eukaryotic E3s. Furthermore, we show that a glutamate residue on E3 is involved in catalyzing ubiquitin transfer from E3 to the substrate, but not from E2 to E3. Together, these results provide mechanistic insights into the ubiquitin pathway and a framework for understanding molecular mimicry in bacterial pathogenesis.« less
  • In E1-E2-E3 ubiquitin (Ub) conjugation cascades, the E2 first forms a transient E2 {approx} Ub covalent complex and then interacts with an E3 for Ub transfer. For cascades involving E3s in the HECT class, Ub is transferred from an associated E2 to the acceptor cysteine in the HECT domain C lobe. To gain insights into this process, we determined the crystal structure of a complex between the HECT domain of NEDD4L and the E2 UbcH5B bearing a covalently linked Ub at its active site (UbcH5B {approx} Ub). Noncovalent interactions between UbcH5B and the HECT N lobe and between Ub andmore » the HECT domain C lobe lead to an overall compact structure, with the Ub C terminus sandwiched between UbcH5B and HECT domain active sites. The structure suggests a model for E2-to-HECT Ub transfer, in which interactions between a donor Ub and an acceptor domain constrain upstream and downstream enzymes for conjugation.« less