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

Kajikawa, Mizuho, Ose, Toyoyuki, Fukunaga, Yuko, Okabe, Yuki, Matsumoto, Naoki, Yonezawa, Kento, Shimizu, Nobutaka, Kollnberger, Simon, Kasahara, Masanori and Maenaka, Katsumi 2018. Structure of MHC class I-like MILL2 reveals heparan-sulfate binding and interdomain flexibility. Nature Communications 9 (1) , 4330. 10.1038/s41467-018-06797-8

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Abstract

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 Å resolution, revealing an organization similar to classical MHC class I. However, the α1-α2 domains are not tightly fixed on the α3-β2m domains, indicating unusual interdomain flexibility. The groove between the two helices in the α1-α2 domains is too narrow to permit ligand binding. Notably, an unusual basic patch on the α3 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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 2041-1723
Date of First Compliant Deposit: 24 January 2019
Date of Acceptance: 27 September 2018
Last Modified: 24 Jan 2019 14:47
URI: http://orca.cf.ac.uk/id/eprint/118597

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