open access

https://hdl.handle.net/2115/72071

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

英語

2018-10-18

Nature Publishing Group

Nature communications

9

4330

The MILL family, composed of MILL1 and MILL2, is a group of nonclassical MHC class I molecules that occur in some orders of mammals. It has been reported that mouse MILL2 is involved in wound healing; however, the molecular mechanisms remain unknown. Here, we determine the crystal structure of MILL2 at 2.15 angstrom resolution, revealing an organization similar to classical MHC class I. However, the alpha 1-alpha 2 domains are not tightly fixed on the alpha 3-beta 2m domains, indicating unusual interdomain flexibility. The groove between the two helices in the alpha 1-alpha 2 domains is too narrow to permit ligand binding. Notably, an unusual basic patch on the alpha 3 domain is involved in the binding to heparan sulfate which is essential for MILL2 interactions with fibroblasts. These findings suggest that MILL2 has a unique structural architecture and physiological role, with binding to heparan sulfate proteoglycans on fibroblasts possibly regulating cellular recruitment in biological events.

学術雑誌論文

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Creative Commons Attribution 4.0 International

2041-1723