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Title: A small protein inhibits proliferating cell nuclear antigen by breaking the DNA clamp

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 » inhibition by TIP.« less
Authors:
 [1] ;  [1] ;  [2] ;  [3] ;  [1] ;  [1] ;  [1]
  1. Univ. of Maryland and the National Institute of Standards and Technology, Rockville, MD (United States)
  2. Univ. of Maryland and the National Institute of Standards and Technology, Rockville, MD (United States); Third Institute of Oceanography, Fujian (China)
  3. Brookhaven National Lab. (BNL), Upton, NY (United States)
Publication Date:
Report Number(s):
BNL-112068-2016-JA
Journal ID: ISSN 0305-1048
Grant/Contract Number:
SC00112704
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
Research Org:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; DNA replication; flap endonuclease 1; proliferating cell nuclear antigen
OSTI Identifier:
1340349