A small protein inhibits proliferating cell nuclear antigen by breaking the DNA clamp
Abstract
Here, proliferating cell nuclear antigen (PCNA) forms a trimeric ring that encircles duplex DNA and acts as an anchor for a number of proteins involved in DNA metabolic processes. PCNA has two structurally similar domains (I and II) linked by a long loop (inter-domain connector loop, IDCL) on the outside of each monomer of the trimeric structure that makes up the DNA clamp. All proteins that bind to PCNA do so via a PCNA-interacting peptide (PIP) motif that binds near the IDCL. A small protein, called TIP, binds to PCNA and inhibits PCNA-dependent activities although it does not contain a canonical PIP motif. The X-ray crystal structure of TIP bound to PCNA reveals that TIP binds to the canonical PIP interaction site, but also extends beyond it through a helix that relocates the IDCL. TIP alters the relationship between domains I and II within the PCNA monomer such that the trimeric ring structure is broken, while the individual domains largely retain their native structure. Small angle X-ray scattering (SAXS) confirms the disruption of the PCNA trimer upon addition of the TIP protein in solution and together with the X-ray crystal data, provides a structural basis for the mechanism of PCNAmore »
- Authors:
-
- Univ. of Maryland and the National Institute of Standards and Technology, Rockville, MD (United States)
- Univ. of Maryland and the National Institute of Standards and Technology, Rockville, MD (United States); Third Institute of Oceanography, Fujian (China)
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Publication Date:
- Research Org.:
- Brookhaven National Laboratory (BNL), Upton, NY (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1340349
- Report Number(s):
- BNL-112068-2016-JA
Journal ID: ISSN 0305-1048
- Grant/Contract Number:
- SC00112704
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nucleic Acids Research
- Additional Journal Information:
- Journal Volume: 44; Journal Issue: 13; Journal ID: ISSN 0305-1048
- Publisher:
- Oxford University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 36 MATERIALS SCIENCE; DNA replication; flap endonuclease 1; proliferating cell nuclear antigen
Citation Formats
Altieri, Amanda S., Ladner, Jane E., Li, Zhuo, Robinson, Howard, Sallman, Zahur F., Marino, John P., and Kelman, Zvi. A small protein inhibits proliferating cell nuclear antigen by breaking the DNA clamp. United States: N. p., 2016.
Web. doi:10.1093/nar/gkw351.
Altieri, Amanda S., Ladner, Jane E., Li, Zhuo, Robinson, Howard, Sallman, Zahur F., Marino, John P., & Kelman, Zvi. A small protein inhibits proliferating cell nuclear antigen by breaking the DNA clamp. United States. https://doi.org/10.1093/nar/gkw351
Altieri, Amanda S., Ladner, Jane E., Li, Zhuo, Robinson, Howard, Sallman, Zahur F., Marino, John P., and Kelman, Zvi. Tue .
"A small protein inhibits proliferating cell nuclear antigen by breaking the DNA clamp". United States. https://doi.org/10.1093/nar/gkw351. https://www.osti.gov/servlets/purl/1340349.
@article{osti_1340349,
title = {A small protein inhibits proliferating cell nuclear antigen by breaking the DNA clamp},
author = {Altieri, Amanda S. and Ladner, Jane E. and Li, Zhuo and Robinson, Howard and Sallman, Zahur F. and Marino, John P. and Kelman, Zvi},
abstractNote = {Here, proliferating cell nuclear antigen (PCNA) forms a trimeric ring that encircles duplex DNA and acts as an anchor for a number of proteins involved in DNA metabolic processes. PCNA has two structurally similar domains (I and II) linked by a long loop (inter-domain connector loop, IDCL) on the outside of each monomer of the trimeric structure that makes up the DNA clamp. All proteins that bind to PCNA do so via a PCNA-interacting peptide (PIP) motif that binds near the IDCL. A small protein, called TIP, binds to PCNA and inhibits PCNA-dependent activities although it does not contain a canonical PIP motif. The X-ray crystal structure of TIP bound to PCNA reveals that TIP binds to the canonical PIP interaction site, but also extends beyond it through a helix that relocates the IDCL. TIP alters the relationship between domains I and II within the PCNA monomer such that the trimeric ring structure is broken, while the individual domains largely retain their native structure. Small angle X-ray scattering (SAXS) confirms the disruption of the PCNA trimer upon addition of the TIP protein in solution and together with the X-ray crystal data, provides a structural basis for the mechanism of PCNA inhibition by TIP.},
doi = {10.1093/nar/gkw351},
journal = {Nucleic Acids Research},
number = 13,
volume = 44,
place = {United States},
year = {Tue May 03 00:00:00 EDT 2016},
month = {Tue May 03 00:00:00 EDT 2016}
}
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Works referencing / citing this record:
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