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From Proteopedia
Crystal structure of human paired immunoglobulin-like type 2 receptor alpha with synthesized glycopeptide I
Structural highlights
Function[PILRA_HUMAN] Paired receptors consist of highly related activating and inhibitory receptors and are widely involved in the regulation of the immune system. PILRA is thought to act as a cellular signaling inhibitory receptor by recruiting cytoplasmic phosphatases like PTPN6/SHP-1 and PTPN11/SHP-2 via their SH2 domains that block signal transduction through dephosphorylation of signaling molecules. Receptor for PIANP.[1] [2] [3] [NOS3_HUMAN] Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.[4] Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.[5] Publication Abstract from PubMedBefore entering host cells, herpes simplex virus-1 uses its envelope glycoprotein B to bind paired immunoglobulin-like type 2 receptor alpha (PILRalpha) on immune cells. PILRalpha belongs to the Siglec (sialic acid (SA)-binding immunoglobulin-like lectin)-like family, members of which bind SA. PILRalpha 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 PILRalpha 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 PILRalpha binding was largely unclear. Here, we chemically synthesized glycopeptide derivatives and determined the thermodynamic parameters of their interaction with PILRalpha. 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 PILRalpha 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 PILRalpha and for the rational design of herpes simplex virus-1 entry inhibitors. Structural and thermodynamic analyses reveal critical features of glycopeptide recognition by the human PILRalpha immune cell receptor.,Furukawa A, Kakita K, Yamada T, Ishizuka M, Sakamoto J, Hatori N, Maeda N, Ohsaka F, Saitoh T, Nomura T, Kuroki K, Nambu H, Arase H, Matsunaga S, Anada M, Ose T, Hashimoto S, Maenaka K J Biol Chem. 2017 Dec 22;292(51):21128-21136. doi: 10.1074/jbc.M117.799239. Epub , 2017 Oct 18. PMID:29046357[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Anada, M | Arase, H | Furukawa, A | Hashimoto, S | Hatori, N | Ishizuka, M | Kakita, K | Kuroki, K | Maeda, N | Maenaka, K | Matsunaga, H | Nambu, H | Nomura, T | Ohsaka, F | Ose, T | Saitoh, T | Sakamoto, J | Yamada, T | Glycopeptide | Immune receptor | Immune system | Membrane protein | Viral entry inhibitor
