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Title: Insights into links between autophagy and the ubiquitin system from the structure of LC3B bound to the LIR motif from the E3 ligase NEDD4: Crystal Structure of LC3B Bound to LIR from NEDD4

Authors:
 [1];  [2];  [1];  [3]
  1. Department of Structural Biology, St. Jude Children's Research Hospital, Memphis Tennessee 38105
  2. Department of Structural Biology, St. Jude Children's Research Hospital, Memphis Tennessee 38105; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis Tennessee 38103
  3. Department of Structural Biology, St. Jude Children's Research Hospital, Memphis Tennessee 38105; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis Tennessee 38103; Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis Tennessee 38105
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
DOE - BASIC ENERGY SCIENCESNIHHHMI
OSTI Identifier:
1374615
Resource Type:
Journal Article
Resource Relation:
Journal Name: Protein Science; Journal Volume: 26; Journal Issue: 8
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Qiu, Yu, Zheng, Yumei, Wu, Kuen-Phon, and Schulman, Brenda A. Insights into links between autophagy and the ubiquitin system from the structure of LC3B bound to the LIR motif from the E3 ligase NEDD4: Crystal Structure of LC3B Bound to LIR from NEDD4. United States: N. p., 2017. Web. doi:10.1002/pro.3186.
Qiu, Yu, Zheng, Yumei, Wu, Kuen-Phon, & Schulman, Brenda A. Insights into links between autophagy and the ubiquitin system from the structure of LC3B bound to the LIR motif from the E3 ligase NEDD4: Crystal Structure of LC3B Bound to LIR from NEDD4. United States. doi:10.1002/pro.3186.
Qiu, Yu, Zheng, Yumei, Wu, Kuen-Phon, and Schulman, Brenda A. 2017. "Insights into links between autophagy and the ubiquitin system from the structure of LC3B bound to the LIR motif from the E3 ligase NEDD4: Crystal Structure of LC3B Bound to LIR from NEDD4". United States. doi:10.1002/pro.3186.
@article{osti_1374615,
title = {Insights into links between autophagy and the ubiquitin system from the structure of LC3B bound to the LIR motif from the E3 ligase NEDD4: Crystal Structure of LC3B Bound to LIR from NEDD4},
author = {Qiu, Yu and Zheng, Yumei and Wu, Kuen-Phon and Schulman, Brenda A.},
abstractNote = {},
doi = {10.1002/pro.3186},
journal = {Protein Science},
number = 8,
volume = 26,
place = {United States},
year = 2017,
month = 6
}
  • No abstract prepared.
  • The first crystallographic study of an isolated WW domain is reported. Single crystals of the WW4 domain of the Nedd4-2 ubiquitin–protein ligase contain a high solvent content of 74% and diffract X-rays to 2.5 Å resolution. Ubiquitin-mediated protein modification via covalent attachment of ubiquitin has emerged as one of the most common regulatory processes in all eukaryotes. Nedd4-2, closely related to neuronal precursor cell-expressed developmentally down-regulated 4 (Nedd4), is a multimodular ubiquitin–protein ligase comprised of four WW domains and a Hect domain. The WW domains recognize the proline-rich motifs on the multi-subunit amiloride-sensitive epithelial sodium channel (ENaC). To gain insightsmore » into the binding of the WW domain to proline-rich peptides, a protein fragment (78 amino acids) containing the fourth WW domain (WW4) of the Nedd4-2 protein was purified and crystallized and X-ray diffraction data were collected. A data set was obtained to 2.5 Å resolution from a cryocooled single crystal at a synchrotron source. The crystals belong to the tetragonal space group P4{sub 1}2{sub 1}2 (or P4{sub 3}2{sub 1}2), with unit-cell parameters a = b = 113.43, c = 103.21 Å. Analysis of the self-rotation function suggests the presence of four WW4 molecules in the asymmetric unit, with a high unit-cell solvent content of 74%.« less
  • E1 ubiquitin-activating enzymes (UBAs) are large multidomain proteins that catalyze formation of a thioester bond between the terminal carboxylate of a ubiquitin or ubiquitin-like modifier (UBL) and a conserved cysteine in an E2 protein, producing reactive ubiquityl units for subsequent ligation to substrate lysines. Two important E1 reaction intermediates have been identified: a ubiquityl-adenylate phosphoester and a ubiquityl-enzyme thioester. However, the mechanism of thioester bond formation and its subsequent transfer to an E2 enzyme remains poorly understood. We have determined the crystal structure of the human UFM1 (ubiquitin-fold modifier 1) E1-activating enzyme UBA5, bound to ATP, revealing a structure thatmore » shares similarities with both large canonical E1 enzymes and smaller ancestral E1-like enzymes. In contrast to other E1 active site cysteines, which are in a variably sized domain that is separate and flexible relative to the adenylation domain, the catalytic cysteine of UBA5 (Cys{sup 250}) is part of the adenylation domain in an {alpha}-helical motif. The novel position of the UBA5 catalytic cysteine and conformational changes associated with ATP binding provides insight into the possible mechanisms through which the ubiquityl-enzyme thioester is formed. These studies reveal structural features that further our understanding of the UBA5 enzyme reaction mechanism and provide insight into the evolution of ubiquitin activation.« less