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Structural and thermodynamic analyses reveal critical features of glycopeptide recognition by the human PILR alpha immune cell receptor

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Title: Structural and thermodynamic analyses reveal critical features of glycopeptide recognition by the human PILR alpha immune cell receptor
Authors: Furukawa, Atsushi Browse this author
Kakita, Kosuke Browse this author
Yamada, Tomoki Browse this author
Ishizuka, Mikihiro Browse this author
Sakamoto, Jiro Browse this author
Hatori, Nanao Browse this author
Maeda, Naoyoshi Browse this author
Ohsaka, Fumina Browse this author
Saitoh, Takashi Browse this author
Nomura, Takao Browse this author
Kuroki, Kimiko Browse this author
Nambu, Hisanori Browse this author
Arase, Hisashi Browse this author
Matsunaga, Shigeki Browse this author
Anada, Masahiro Browse this author
Ose, Toyoyuki Browse this author
Hashimoto, Shunichi Browse this author
Maenaka, Katsumi Browse this author →KAKEN DB
Issue Date: 22-Dec-2017
Publisher: American Society for Biochemistry and Molecular Biology (ASBMB)
Journal Title: Journal of Biological Chemistry (JBC)
Volume: 292
Issue: 51
Start Page: 21128
End Page: 21136
Publisher DOI: 10.1074/jbc.M117.799239
Abstract: Before entering host cells, herpes simplex virus-1 uses its envelope glycoprotein B to bind paired immunoglobulin-like type 2 receptor alpha (PILR alpha) on immune cells. PILR alpha belongs to the Siglec (sialic acid (SA)-binding immunoglobulin-like lectin)- like family, members of which bind SA. PILR alpha is the only Siglec member to recognize not only the sialylated O-linked sugar T antigen (sTn) but also its attached peptide region. We previously determined the crystal structure of PILR alpha complexed with the sTn-linked glycopeptide of glycoprotein B, revealing the simultaneous recognition of sTn and peptide by the receptor. However, the contribution of each glycopeptide component to PILR alpha binding was largely unclear. Here, we chemically synthesized glycopeptide derivatives and determined the thermodynamic parameters of their interaction with PILR alpha. We show that glycopeptides with different sugar units linking SA and peptides (i.e. "GlcNAc-type" and "deoxy-GlcNAc-type" glycopeptides) have lower affinity and more enthalpy-driven binding than the wild type (i.e. GalNAc-type glycopeptide). The crystal structures of PILR alpha complexed with these glycopeptides highlighted the importance of stereochemical positioning of the O4 atom of the sugar moiety. These results provide insights both for understanding the unique O-glycosylated peptide recognition by the PILR alpha and for the rational design of herpes simplex virus-1 entry inhibitors.
Rights: This research was originally published in JBC. Furukawa, Atsushi et al. Structural and thermodynamic analyses reveal critical features of glycopeptide recognition by the human PILR alpha immune cell receptor. Journal of Biological Chemistry. 2017; 292:21128-21136. © the American Society for Biochemistry and Molecular Biology.
Type: article
URI: http://hdl.handle.net/2115/72215
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 前仲 勝実

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