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

Journal Article · Tue May 03 00:00:00 EDT 2016 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkw351· OSTI ID:1346225

Altieri, Amanda S.; Ladner, Jane E.; Li, Zhuo; Robinson, Howard; Sallman, Zahur F.; Marino, John P.; Kelman, Zvi

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.

• Research Organization: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE; National Institute of Standards and Technology (NIST)
• OSTI ID: 1346225
• Journal Information: Nucleic Acids Research, Vol. 44, Issue 13; ISSN 0305-1048
• Publisher: Oxford University Press
• Country of Publication: United States
• Language: ENGLISH

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59 BASIC BIOLOGICAL SCIENCES