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Originally published In Press as doi:10.1074/jbc.M603076200 on May 3, 2006
J. Biol. Chem., Vol. 281, Issue 28, 19536-19544, July 14, 2006
Crystal Structure of the Human Monocyte-activating Receptor, "Group 2" Leukocyte Ig-like Receptor A5 (LILRA5/LIR9/ILT11)*
Mitsunori Shiroishi,
Mizuho Kajikawa,
Kimiko Kuroki,
Toyoyuki Ose,
Daisuke Kohda1, and
Katsumi Maenaka2
From the
Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Human leukocyte Ig-like receptor B1 (LILRB1) and B2 (LILRB2) belong to "Group 1" receptors and recognize a broad range of major histocompatibility complex class I molecules (MHCIs). In contrast, "Group 2" receptors show low similarity with LILRB1/B2, and their ligands remain to be identified. To date, the structural and functional characteristics of Group 2 LILRs are poorly understood. Here we report the crystal structure of the extracellular domain of LILRA5, which is an activating Group 2 LILR expressed on monocytes and neutrophils. Unexpectedly, the structure showed large changes in structural conformation and charge distribution in the region corresponding to the MHCI binding site of LILRB1/B2, which are also distinct from killer cell Ig-like receptors and Fc receptors. These changes probably confer the structural hindrance for the MHCI binding, and their key amino acid substitutions are well conserved in Group 2 LILRs. Consistently, the surface plasmon resonance and flow cytometric analyses demonstrated that LILRA5 exhibited no affinities to all tested MHCIs. These results raised the possibility that LILRA5 as well as Group 2 LILRs do not play a role in any MHCI recognition but could possibly bind to non-MHCI ligand(s) on the target cells to provide a novel immune regulation mechanism.
Received for publication, March 31, 2006
, and in revised form, April 26, 2006.
The atomic coordinates and structure factors (code 2D3V) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
* This work was supported by research fellowships and a research grant of the Japan Society for the Promotion of Science for young scientists (to M. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1 and Table S1.
1 Supported in part by the Ministry of Education, Science, Sports, Culture and Technology of Japan and the Protein 3000 project.
2 Supported in part by the Ministry of Education, Science, Sports, Culture and Technology of Japan, the Protein 3000 project, and the Kanae foundation. To whom correspondence should be addressed: Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Tel.: 81-92-642-6969; Fax: 81-92-642-6764; E-mail: kmaenaka{at}bioreg.kyushu-u.ac.jp.

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Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
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