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Cited by 112Ubiquitin and proteasome pathwaysSupramolecular Self-Assembly in MaterialsProtein Structure and Dynamics

Control of biochemical reactions through supramolecular RING domain self-assembly

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Kentsis, Alex, Gordon, Ronald E., Borden, Katherine L. B.·2002·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.202608799PMC PMC137729
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Abstract

RING domains act in a variety of unrelated biochemical reactions, with many of these domains forming key parts of supramolecular assemblies in cells. Here, we observe that purified RINGs from a variety of functionally unrelated proteins, including promyelocytic leukemia protein, KAP-1/TIF1β, Z, Mel18, breast cancer susceptibility gene product 1 (BRCA1), and BRCA1-associated RING domain (BARD1), self-assemble into supramolecular structures in vitro that resemble those they form in cells. RING bodies form polyvalent binding surfaces and scaffold multiple partner proteins. Separation of RING bodies from monomers reveals that self-assembly controls and amplifies their specific activities in two unrelated biochemistries: reduction of 5′ mRNA cap affinity of eIF4E by promyelocytic leukemia protein and Z, and E3 ubiquitin conjugation activity of BARD1:BRCA1. Functional significance of self-assembly is underscored by partial restoration of assembly and E3 activity of cancer predisposing BRCA1 mutant by forced oligomerization. RING self-assembly creates bodies that act structurally as polyvalent scaffolds, thermodynamically by amplifying activities of partner proteins, and catalytically by spatiotemporal coupling of enzymatic reactions. These studies reveal a general paradigm of how supramolecular structures may function in cells.

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Authors
Kentsis, A., Gordon, R. E., & Borden, K. L. B.
Affiliations
  • New York University (US)
  • California Institute of Technology (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2002-11-18
Volume
99
Issue
24
Pages
15404-15409
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.202608799
PMC
PMC137729
OpenAlex
W2109838706
Cited by
112
References
27
Citations by year
2026: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 3 · 2016: 2 · 2014: 4 · 2013: 6 · 2012: 6
FWCI
3.95
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Leukemia and Lymphoma Society
  • University of Washington
  • University of Montana
  • National Institutes of Health (80728)
  • National Cancer Institute (R01CA088991, CA88991, CA 80728, R01CA080728)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
RING domain, protein self-assembly, supramolecular self-assembly, promyelocytic leukemia protein, BRCA1, BARD1, E3 ubiquitin ligase, protein oligomerization
MeSH terms
Promyelocytic Leukemia Protein, Tripartite Motif-Containing Protein 28, Animals, Breast Neoplasms, Carrier Proteins, Catalysis, Cattle, Cells, DNA-Binding Proteins, Humans, Ligases, Membrane Proteins, Models, Biological, Mutation, Neoplasm Proteins, Nuclear Proteins, Protein Binding, Rabbits, Repressor Proteins, RNA Caps, Structure-Activity Relationship, Thermodynamics, Transcription Factors, Zinc, Protein Structure, Tertiary, Protein Folding, Immediate-Early Proteins, BRCA1 Protein, Genes, BRCA1, Tumor Suppressor Proteins, Ubiquitin, Eukaryotic Initiation Factor-4E, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Macromolecular Substances, Intracellular Signaling Peptides and Proteins, Mice

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