publication . Article . Other literature type . 2019

Structural basis for adenylation and thioester bond formation in the ubiquitin E1

Derek S. Tan; Derek S. Tan; Christopher D. Lima; Christopher D. Lima; Zachary S. Hann; Zachary S. Hann; Xuequan Lu; Michaelyn C. Lux; Michaelyn C. Lux; Shaun K. Olsen; ...
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Open Access English
  • Published: 01 Jun 2019 Journal: Proceedings of the National Academy of Sciences of the United States of America, volume 116, issue 31, pages 15,475-15,484 (issn: 0027-8424, eissn: 1091-6490, Copyright policy)
  • Publisher: National Academy of Sciences
Abstract
Significance Posttranslational protein modification by ubiquitin (Ub) regulates aspects of biology, including protein turnover and the cell cycle. Proteins and enzymes that promote Ub conjugation are therapeutic targets because they are sometimes dysregulated in cancer, neurodegenerative diseases, and other disorders. Ub conjugation is initiated by a Ub-activating enzyme that adopts different conformations to catalyze Ub activation, Ub-activating enzyme thioester bond formation, and thioester bond transfer to Ub-conjugating enzymes. Here, we illuminate 2 uncharacterized states for Ub-activating enzyme, one bound to pyrophosphate prior to thioester bond formation...
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doi: 10.1073/pnas.1905488116
pmc: PMC6681703
pmid: 31235585
Subjects
Medical Subject Headings: lipids (amino acids, peptides, and proteins)animal structuresorganic chemicals
free text keywords: PNAS Plus, Biological Sciences, Biochemistry, ubiquitin, adenylation, thioester, X-ray, E1, Multidisciplinary, Chemistry, Adenylylation, chemistry.chemical_classification, Stereochemistry, Enzyme, Pyrophosphate, chemistry.chemical_compound, Schizosaccharomyces pombe, biology.organism_classification, biology, Cysteine, Covalent bond, biology.protein
Related Organizations
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Funded by
NIH| Structural and Functional Studies of Eukaryotic Exosomes
Project
Structural and Functional Studies of Eukaryotic Exosomes
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01GM079196-07
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
, NIH| Pixel Array Detector for X-ray Crystallography
Project
Pixel Array Detector for X-ray Crystallography
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1S10RR029205-01
  • Funding stream: NATIONAL CENTER FOR RESEARCH RESOURCES
, NIH| Structural Studies of SUMO Protein Modification
Project
Structural Studies of SUMO Protein Modification
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01GM065872-12
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
, NIH| NE-CAT Center for Advanced Macromolecular Crystallography
Project
NE-CAT Center for Advanced Macromolecular Crystallography
  • Funder: National Institutes of Health (NIH)
  • Project Code: 4P41GM103403-14
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
, NIH| Rational Design of Adenylation Enzyme Inhibitors
Project
Rational Design of Adenylation Enzyme Inhibitors
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01GM100477-08
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
View more
Download fromView all 3 versions
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Article . 2019
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72 references, page 1 of 5

1 Taherbhoy A. M., Schulman B. A., Kaiser S. E., Ubiquitin-like modifiers. Essays Biochem.52, 51–63 (2012).22708563 [PubMed]

2 Streich F. C.Jr, Lima C. D., Structural and functional insights to ubiquitin-like protein conjugation. Annu. Rev. Biophys.43, 357–379 (2014).24773014 [OpenAIRE] [PubMed]

3 Wang X., Herr R. A., Hansen T. H., Ubiquitination of substrates by esterification. Traffic 13, 19–24 (2012).21883762 [OpenAIRE] [PubMed]

4 Hershko A., Ciechanover A., The ubiquitin system. Annu. Rev. Biochem.67, 425–479 (1998).9759494 [OpenAIRE] [PubMed]

5 Schulman B. A., Harper J. W., Ubiquitin-like protein activation by E1 enzymes: The apex for downstream signalling pathways. Nat. Rev. Mol. Cell Biol.10, 319–331 (2009).19352404 [OpenAIRE] [PubMed]

6 van Wijk S. J. L., Timmers H. T. M., The family of ubiquitin-conjugating enzymes (E2s): Deciding between life and death of proteins. FASEB J.24, 981–993 (2010).19940261 [OpenAIRE] [PubMed]

7 Gareau J. R., Lima C. D., The SUMO pathway: Emerging mechanisms that shape specificity, conjugation and recognition. Nat. Rev. Mol. Cell Biol.11, 861–871 (2010).21102611 [OpenAIRE] [PubMed]

8 Tanaka K., Suzuki T., Chiba T., The ligation systems for ubiquitin and ubiquitin-like proteins. Mol. Cells 8, 503–512 (1998).9856335 [PubMed]

9 Buetow L., Huang D. T., Structural insights into the catalysis and regulation of E3 ubiquitin ligases. Nat. Rev. Mol. Cell Biol.17, 626–642 (2016).27485899 [OpenAIRE] [PubMed]

10 Cappadocia L., Lima C. D., Ubiquitin-like protein conjugation: Structures, chemistry, and mechanism. Chem. Rev.118, 889–918 (2018).28234446 [OpenAIRE] [PubMed]

11 Mevissen T. E. T., Komander D., Mechanisms of deubiquitinase specificity and regulation. Annu. Rev. Biochem.86, 159–192 (2017).28498721 [OpenAIRE] [PubMed]

12 Freemont P. S., Hanson I. M., Trowsdale J., A novel cysteine-rich sequence motif. Cell 64, 483–484 (1991).1991318 [PubMed]

13 Huibregtse J. M., Scheffner M., Beaudenon S., Howley P. M., A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc. Natl. Acad. Sci. U.S.A.92, 2563–2567 (1995).7708685 [OpenAIRE] [PubMed]

14 Wenzel D. M., Lissounov A., Brzovic P. S., Klevit R. E., UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 474, 105–108 (2011).21532592 [OpenAIRE] [PubMed]

15 Sundlov J. A., Shi C., Wilson D. J., Aldrich C. C., Gulick A. M., Structural and functional investigation of the intermolecular interaction between NRPS adenylation and carrier protein domains. Chem. Biol.19, 188–198 (2012).22365602 [OpenAIRE] [PubMed]

72 references, page 1 of 5
Related research
Abstract
Significance Posttranslational protein modification by ubiquitin (Ub) regulates aspects of biology, including protein turnover and the cell cycle. Proteins and enzymes that promote Ub conjugation are therapeutic targets because they are sometimes dysregulated in cancer, neurodegenerative diseases, and other disorders. Ub conjugation is initiated by a Ub-activating enzyme that adopts different conformations to catalyze Ub activation, Ub-activating enzyme thioester bond formation, and thioester bond transfer to Ub-conjugating enzymes. Here, we illuminate 2 uncharacterized states for Ub-activating enzyme, one bound to pyrophosphate prior to thioester bond formation...
Read more
doi: 10.1073/pnas.1905488116
pmc: PMC6681703
pmid: 31235585
Subjects
Medical Subject Headings: lipids (amino acids, peptides, and proteins)animal structuresorganic chemicals
free text keywords: PNAS Plus, Biological Sciences, Biochemistry, ubiquitin, adenylation, thioester, X-ray, E1, Multidisciplinary, Chemistry, Adenylylation, chemistry.chemical_classification, Stereochemistry, Enzyme, Pyrophosphate, chemistry.chemical_compound, Schizosaccharomyces pombe, biology.organism_classification, biology, Cysteine, Covalent bond, biology.protein
Related Organizations
View more
Funded by
NIH| Structural and Functional Studies of Eukaryotic Exosomes
Project
Structural and Functional Studies of Eukaryotic Exosomes
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01GM079196-07
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
, NIH| Pixel Array Detector for X-ray Crystallography
Project
Pixel Array Detector for X-ray Crystallography
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1S10RR029205-01
  • Funding stream: NATIONAL CENTER FOR RESEARCH RESOURCES
, NIH| Structural Studies of SUMO Protein Modification
Project
Structural Studies of SUMO Protein Modification
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01GM065872-12
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
, NIH| NE-CAT Center for Advanced Macromolecular Crystallography
Project
NE-CAT Center for Advanced Macromolecular Crystallography
  • Funder: National Institutes of Health (NIH)
  • Project Code: 4P41GM103403-14
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
, NIH| Rational Design of Adenylation Enzyme Inhibitors
Project
Rational Design of Adenylation Enzyme Inhibitors
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01GM100477-08
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
View more
Download fromView all 3 versions
Europe PubMed Central
Article . 2019
Provider: PubMed Central
Proceedings of the National Academy of Sciences
Article
Provider: UnpayWall
http://dx.doi.org/10.1073/pnas...
Other literature type . 2019
Provider: Datacite
Proceedings of the National Academy of Sciences
Article
Provider: Microsoft Academic Graph
View more
72 references, page 1 of 5

1 Taherbhoy A. M., Schulman B. A., Kaiser S. E., Ubiquitin-like modifiers. Essays Biochem.52, 51–63 (2012).22708563 [PubMed]

2 Streich F. C.Jr, Lima C. D., Structural and functional insights to ubiquitin-like protein conjugation. Annu. Rev. Biophys.43, 357–379 (2014).24773014 [OpenAIRE] [PubMed]

3 Wang X., Herr R. A., Hansen T. H., Ubiquitination of substrates by esterification. Traffic 13, 19–24 (2012).21883762 [OpenAIRE] [PubMed]

4 Hershko A., Ciechanover A., The ubiquitin system. Annu. Rev. Biochem.67, 425–479 (1998).9759494 [OpenAIRE] [PubMed]

5 Schulman B. A., Harper J. W., Ubiquitin-like protein activation by E1 enzymes: The apex for downstream signalling pathways. Nat. Rev. Mol. Cell Biol.10, 319–331 (2009).19352404 [OpenAIRE] [PubMed]

6 van Wijk S. J. L., Timmers H. T. M., The family of ubiquitin-conjugating enzymes (E2s): Deciding between life and death of proteins. FASEB J.24, 981–993 (2010).19940261 [OpenAIRE] [PubMed]

7 Gareau J. R., Lima C. D., The SUMO pathway: Emerging mechanisms that shape specificity, conjugation and recognition. Nat. Rev. Mol. Cell Biol.11, 861–871 (2010).21102611 [OpenAIRE] [PubMed]

8 Tanaka K., Suzuki T., Chiba T., The ligation systems for ubiquitin and ubiquitin-like proteins. Mol. Cells 8, 503–512 (1998).9856335 [PubMed]

9 Buetow L., Huang D. T., Structural insights into the catalysis and regulation of E3 ubiquitin ligases. Nat. Rev. Mol. Cell Biol.17, 626–642 (2016).27485899 [OpenAIRE] [PubMed]

10 Cappadocia L., Lima C. D., Ubiquitin-like protein conjugation: Structures, chemistry, and mechanism. Chem. Rev.118, 889–918 (2018).28234446 [OpenAIRE] [PubMed]

11 Mevissen T. E. T., Komander D., Mechanisms of deubiquitinase specificity and regulation. Annu. Rev. Biochem.86, 159–192 (2017).28498721 [OpenAIRE] [PubMed]

12 Freemont P. S., Hanson I. M., Trowsdale J., A novel cysteine-rich sequence motif. Cell 64, 483–484 (1991).1991318 [PubMed]

13 Huibregtse J. M., Scheffner M., Beaudenon S., Howley P. M., A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc. Natl. Acad. Sci. U.S.A.92, 2563–2567 (1995).7708685 [OpenAIRE] [PubMed]

14 Wenzel D. M., Lissounov A., Brzovic P. S., Klevit R. E., UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 474, 105–108 (2011).21532592 [OpenAIRE] [PubMed]

15 Sundlov J. A., Shi C., Wilson D. J., Aldrich C. C., Gulick A. M., Structural and functional investigation of the intermolecular interaction between NRPS adenylation and carrier protein domains. Chem. Biol.19, 188–198 (2012).22365602 [OpenAIRE] [PubMed]

72 references, page 1 of 5
Related research
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