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Updated: Jan 23, 2026

Crystal Structure of the N-terminal Domain of Ryanodine Receptor from Plutella xylostella
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Solution structure, dynamics and function investigation of Kringle domain of human receptor tyrosine kinase-like

Xiaofang Ma1,2, Bin Liu1,2, Jiahui Yang3

  • 1State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming, People's Republic of China.

Journal of Biomolecular Structure & Dynamics
|June 25, 2019
PubMed

Insights

The Kringle domain of Receptor tyrosine kinase-like orphan receptor 1 (ROR1) has a unique structure, suggesting interactions with non-canonical ligands. This study reveals ROR1-Kringle domain dynamics and binding interfaces, crucial for cancer therapy development.

Area of Science:

  • Structural Biology
  • Biochemistry
  • Cancer Research

Background:

  • Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a potential cancer therapeutic target.
  • Monoclonal antibodies targeting the ROR1 Kringle (KNG) domain may induce cancer cell apoptosis.

Purpose of the Study:

  • Determine the solution structure of human ROR1-KNG (hROR1-KNG).
  • Investigate hROR1-KNG's dynamic properties and potential binding interfaces.
  • Explore interactions with monoclonal antibodies and ROR2.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy for structure determination and dynamics analysis.
  • Chemical shift perturbation experiments to assess binding interactions.

Main Results:

  • The NMR structure of hROR1-KNG shows an open conformation with unique features at the lysine binding site, suggesting non-canonical ligand interactions.
  • Dynamics analysis revealed local flexibility and conformational exchange, potentially influencing disulfide bond formation and ligand binding.
  • The binding interface for mAb R11 was identified; no direct interaction between hROR1-KNG and hROR2-KNG was observed.

Conclusions:

  • The unique structural and dynamic properties of hROR1-KNG provide a foundation for understanding its biological interactions.
  • Findings are critical for developing targeted cancer therapies involving ROR1.
Keywords:
Kringle domainNMRROR1RTK superfamilydynamics

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