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Updated: Nov 8, 2025

Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique
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Crystal structure and molecular dynamics of human POLDIP2, a multifaceted adaptor protein in metabolism and genome

Anastasija A Kulik1, Klaudia K Maruszczak, Dana C Thomas

  • 1Department of Biological and Geographical Sciences, School of Applied Sciences, University of Huddersfield, Huddersfield, UK.

Protein Science : a Publication of the Protein Society
|April 22, 2021
PubMed

Insights

The crystal structure of Polymerase δ-interacting protein 2 (POLDIP2) reveals a dynamic, two-domain protein. Its flexible regions and central channel likely mediate interactions with diverse cellular partners, explaining its multifaceted roles.

Area of Science:

  • Structural Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Polymerase δ-interacting protein 2 (POLDIP2) is a "moonlighting" protein involved in mitochondrial metabolism and DNA replication/repair.
  • The mechanisms by which POLDIP2 interacts with numerous protein partners remain unclear.

Purpose of the Study:

  • To elucidate the structural basis for POLDIP2's multifaceted protein interactions.
  • To characterize the three-dimensional structure of POLDIP2.

Main Methods:

  • X-ray crystallography (2.8 Å resolution)
  • Circular dichroism (CD) spectroscopy
  • Small-angle X-ray scattering (SAXS)
  • Ab initio modeling
  • Molecular dynamics (MD) simulations

Main Results:

  • POLDIP2 exhibits a compact, two-domain, β-strand-rich globular structure.
  • A tightly packed domain linker creates an extended YccV module, and a central channel with a modified cysteine suggests redox-sensitive conformational changes.
  • MD simulations reveal a dynamic N-terminal region and flexible loops, crucial for partner binding.
  • Complex models with PrimPol and PCNA support the role of N-terminal and loop flexibility in mediating interactions.

Conclusions:

  • The determined structure provides insights into POLDIP2's ability to interact with diverse partners.
  • Structural flexibility, particularly in the N-terminus and loops, is key to POLDIP2's function as a versatile protein hub.
Keywords:
DNA polymerasePCNAPDIP38POLDIP2PrimPolprotein structure

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