| 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)
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