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Human tripartite motif-containing protein 71 NCL-1/HT2A/LIN-41 domain crystal structure and its potential natural

Liqing Lin1, Md Kazy Ebnul Hasan1, Xianfu Gu1

  • 1Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China; Ministry of Education Key Laboratory for Membraneless Organelles and Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China; Hefei National Research Center for Cross-disciplinary Science, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.

International Journal of Biological Macromolecules
|April 3, 2025
PubMed

Insights

The TRIM71 NHL domain binds CDKN1A mRNA, repressing its expression to promote cancer cell proliferation. Researchers identified natural compounds, epigallocatechin gallate and cyanidin 3-O-galactoside, as potential inhibitors for therapeutic development.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • The TRIM71 NHL domain is implicated in cellular processes and dysregulated in cancers and congenital hydrocephalus.
  • Its specific pathways and interaction with CDKN1A remain underexplored, hindering therapeutic target identification.

Purpose of the Study:

  • To elucidate the structural basis of TRIM71 NHL domain interaction with CDKN1A mRNA.
  • To identify potential natural inhibitors of the TRIM71 NHL domain for therapeutic applications.

Main Methods:

  • Expression and purification of TRIM71 NHL domain in insect cells.
  • Determination of crystal structure (PDB ID: 9JUR).
  • Biophysical assays (fluorescence polarization, EMSA, SPR) and molecular dynamics simulations.

Main Results:

  • The crystal structure of the TRIM71 NHL domain was successfully determined.
  • Strong and specific binding of TRIM71 NHL domain to CDKN1A mRNA was confirmed (Kd = 0.42 ± 0.04 μM).
  • Epigallocatechin Gallate and Cyanidin 3-O-galactoside showed significant binding affinities, indicating potential as inhibitors.

Conclusions:

  • The determined crystal structure provides insights into TRIM71 NHL domain's structural features.
  • TRIM71 NHL domain's interaction with CDKN1A mRNA suggests a role in cancer proliferation.
  • Identified phytochemicals offer a basis for developing novel therapeutic strategies targeting TRIM71.
Keywords:
CrystallographyCyanidin-3-O-galactosideEpigallocatechin gallateMD simulationMolecular dockingTRIM71 NHL domain

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