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Resonance assignments for the tandem PWWP-ARID domains of human RBBP1

Weibin Gong1, Xingzhe Yao2,3,4, Qihui Liang1,4

  • 1National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

Biomolecular NMR Assignments
|January 23, 2019
PubMed

Insights

This study reports the first near-complete NMR assignment for the human Retinoblastoma-binding protein 1 (RBBP1) tandem PWWP-ARID domain. This provides crucial structural insights into a key tumor suppressor involved in epigenetic regulation.

Area of Science:

  • Structural Biology
  • Epigenetics
  • Molecular Biology

Background:

  • Retinoblastoma-binding protein 1 (RBBP1), also known as AT-rich interaction domain 4A (ARID4A), is a tumor suppressor.
  • RBBP1 regulates epigenetic programming in conditions like leukemia and Prader-Willi/Angelman syndromes.
  • The ARID domain of RBBP1 exhibits non-specific DNA binding and gene suppression activity, but its structure remains uncharacterized.

Purpose of the Study:

  • To determine the near-complete backbone and side-chain NMR assignment for the human RBBP1 tandem PWWP-ARID domain.
  • To provide foundational structural data for the human RBBP1 ARID domain.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy was employed to assign 1H, 13C, and 15N chemical shifts.
  • A 27 kDa tandem PWWP-ARID domain construct (residues 171-414) was utilized, with a short disordered region removed.
  • Secondary structure was predicted based on the assigned chemical shifts.

Main Results:

  • Near-complete 1H, 13C, 15N backbone and side-chain NMR assignments were achieved for the RBBP1 tandem PWWP-ARID domain.
  • The predicted secondary structure aligns with previously solved structures of the human RBBP1 PWWP domain and homologous ARID domains.
  • This provides the first structural data for the human RBBP1 ARID domain.

Conclusions:

  • The NMR assignment provides essential structural information for the human RBBP1 tandem PWWP-ARID domain.
  • This data serves as a basis for understanding the molecular mechanisms of RBBP1 in epigenetic regulation.
  • The findings contribute to the structural characterization of key proteins involved in tumor suppression and genetic disorders.

Keywords:
ARID domainNMR assignmentsRBBP1Secondary structureTandem domains

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