Related Experiment Video

Updated: Feb 3, 2026

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
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Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis

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Structure of MHC class I-like MILL2 reveals heparan-sulfate binding and interdomain flexibility

Mizuho Kajikawa1,2, Toyoyuki Ose3, Yuko Fukunaga2

  • 1Laboratory of Microbiology, Showa Pharmaceutical University, Machida, Tokyo, 190-8543, Japan.

Nature Communications
|October 20, 2018
PubMed

Insights

The MILL2 protein, a nonclassical MHC class I molecule, has a unique structure that binds to heparan sulfate. This interaction with fibroblasts may regulate cellular recruitment in biological events like wound healing.

Area of Science:

  • Immunology
  • Structural Biology
  • Biochemistry

Background:

  • The MILL family, including MILL1 and MILL2, comprises nonclassical MHC class I molecules found in certain mammals.
  • Mouse MILL2 is implicated in wound healing, but its molecular mechanisms are not understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms of MILL2 in wound healing by determining its crystal structure and identifying its binding interactions.

Main Methods:

  • X-ray crystallography was used to determine the crystal structure of MILL2 at 2.15 Å resolution.
  • Structural analysis focused on domain organization, interdomain flexibility, and potential ligand-binding sites.
  • Biochemical assays investigated the interaction of MILL2 with heparan sulfate and fibroblasts.

Main Results:

  • MILL2 exhibits an overall structure similar to classical MHC class I molecules.
  • Unusual interdomain flexibility was observed between the α1-α2 and α3-β2m domains.
  • The ligand-binding groove is too narrow for typical peptide binding.
  • A unique basic patch on the α3 domain mediates binding to heparan sulfate.

Conclusions:

  • MILL2 possesses a distinct structural architecture and a novel physiological role.
  • MILL2's interaction with heparan sulfate proteoglycans on fibroblasts likely regulates cellular recruitment.
  • This mechanism may be crucial for biological processes such as wound healing.

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