RING Dimerization Links Higher-Order Assembly of TRIM5α to Synthesis of K63-Linked Polyubiquitin
Abstract
Members of the tripartite motif (TRIM) protein family of RING E3 ubiquitin (Ub) ligases promote innate immune responses by catalyzing synthesis of polyubiquitin chains linked through lysine 63 (K63). Here, we investigate the mechanism by which the TRIM5α retroviral restriction factor activates Ubc13, the K63-linkage-specific E2. Structural, biochemical, and functional characterization of the TRIM5α:Ubc13-Ub interactions reveals that activation of the Ubc13-Ub conjugate requires dimerization of the TRIM5α RING domain. Our data explain how higher-order oligomerization of TRIM5α, which is promoted by the interaction with the retroviral capsid, enhances the E3 Ub ligase activity of TRIM5α and contributes to its antiretroviral function. This E3 mechanism, in which RING dimerization is transient and depends on the interaction of the TRIM protein with the ligand, is likely to be conserved in many members of the TRIM family and may have evolved to facilitate recognition of repetitive epitope patterns associated with infection.
- Authors:
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- Contributing Org.:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- OSTI Identifier:
- 1242423
- Alternate Identifier(s):
- OSTI ID: 1208690
- Grant/Contract Number:
- AC02-06CH11357
- Resource Type:
- Journal Article: Published Article
- Journal Name:
- Cell Reports
- Additional Journal Information:
- Journal Name: Cell Reports Journal Volume: 12 Journal Issue: 5; Journal ID: ISSN 2211-1247
- Publisher:
- Elsevier
- Country of Publication:
- Netherlands
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Yudina, Zinaida, Roa, Amanda, Johnson, Rory, Biris, Nikolaos, de Souza Aranha Vieira, Daniel A., Tsiperson, Vladislav, Reszka, Natalia, Taylor, Alexander B., Hart, P. John, Demeler, Borries, Diaz-Griffero, Felipe, and Ivanov, Dmitri N. RING Dimerization Links Higher-Order Assembly of TRIM5α to Synthesis of K63-Linked Polyubiquitin. Netherlands: N. p., 2015.
Web. doi:10.1016/j.celrep.2015.06.072.
Yudina, Zinaida, Roa, Amanda, Johnson, Rory, Biris, Nikolaos, de Souza Aranha Vieira, Daniel A., Tsiperson, Vladislav, Reszka, Natalia, Taylor, Alexander B., Hart, P. John, Demeler, Borries, Diaz-Griffero, Felipe, & Ivanov, Dmitri N. RING Dimerization Links Higher-Order Assembly of TRIM5α to Synthesis of K63-Linked Polyubiquitin. Netherlands. https://doi.org/10.1016/j.celrep.2015.06.072
Yudina, Zinaida, Roa, Amanda, Johnson, Rory, Biris, Nikolaos, de Souza Aranha Vieira, Daniel A., Tsiperson, Vladislav, Reszka, Natalia, Taylor, Alexander B., Hart, P. John, Demeler, Borries, Diaz-Griffero, Felipe, and Ivanov, Dmitri N. 2015.
"RING Dimerization Links Higher-Order Assembly of TRIM5α to Synthesis of K63-Linked Polyubiquitin". Netherlands. https://doi.org/10.1016/j.celrep.2015.06.072.
@article{osti_1242423,
title = {RING Dimerization Links Higher-Order Assembly of TRIM5α to Synthesis of K63-Linked Polyubiquitin},
author = {Yudina, Zinaida and Roa, Amanda and Johnson, Rory and Biris, Nikolaos and de Souza Aranha Vieira, Daniel A. and Tsiperson, Vladislav and Reszka, Natalia and Taylor, Alexander B. and Hart, P. John and Demeler, Borries and Diaz-Griffero, Felipe and Ivanov, Dmitri N.},
abstractNote = {Members of the tripartite motif (TRIM) protein family of RING E3 ubiquitin (Ub) ligases promote innate immune responses by catalyzing synthesis of polyubiquitin chains linked through lysine 63 (K63). Here, we investigate the mechanism by which the TRIM5α retroviral restriction factor activates Ubc13, the K63-linkage-specific E2. Structural, biochemical, and functional characterization of the TRIM5α:Ubc13-Ub interactions reveals that activation of the Ubc13-Ub conjugate requires dimerization of the TRIM5α RING domain. Our data explain how higher-order oligomerization of TRIM5α, which is promoted by the interaction with the retroviral capsid, enhances the E3 Ub ligase activity of TRIM5α and contributes to its antiretroviral function. This E3 mechanism, in which RING dimerization is transient and depends on the interaction of the TRIM protein with the ligand, is likely to be conserved in many members of the TRIM family and may have evolved to facilitate recognition of repetitive epitope patterns associated with infection.},
doi = {10.1016/j.celrep.2015.06.072},
url = {https://www.osti.gov/biblio/1242423},
journal = {Cell Reports},
issn = {2211-1247},
number = 5,
volume = 12,
place = {Netherlands},
year = {Sat Aug 01 00:00:00 EDT 2015},
month = {Sat Aug 01 00:00:00 EDT 2015}
}
Web of Science
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