TY - JOUR
T1 - Structural basis for simultaneous recognition of an O-glycan and its attached peptide of mucin family by immune receptor PILRα
AU - Kuroki, Kimiko
AU - Wang, Jing
AU - Ose, Toyoyuki
AU - Yamaguchi, Munechika
AU - Tabata, Shigekazu
AU - Maita, Nobuo
AU - Nakamura, Seiko
AU - Kajikawa, Mizuho
AU - Kogure, Amane
AU - Satoh, Takeshi
AU - Arase, Hisashi
AU - Maenaka, Katsumi
PY - 2014
Y1 - 2014
N2 - Paired Ig-like type 2 receptor α (PILRα) recognizes a wide range of O-glycosylated mucin and related proteins to regulate broad immune responses. However, the molecular characteristics of these recognitions are largely unknown. Here we show that sialylated O-linked sugar T antigen (sTn) and its attached peptide region are both required for ligand recognition by PILRα. Furthermore, we determined the crystal structures of PILRα and its complex with an sTn and its attached peptide region. The structures show that PILRα exhibits large conformational change to recognize simultaneously both the sTn O-glycan and the compact peptide structure constrained by proline residues. Binding and functional assays support this binding mode. These findings provide significant insight into the binding motif and molecular mechanism (which is distinct from sugar-recognition receptors) by which O-glycosylated mucin proteins with sTn modifications are recognized in the immune system as well as during viral entry.
AB - Paired Ig-like type 2 receptor α (PILRα) recognizes a wide range of O-glycosylated mucin and related proteins to regulate broad immune responses. However, the molecular characteristics of these recognitions are largely unknown. Here we show that sialylated O-linked sugar T antigen (sTn) and its attached peptide region are both required for ligand recognition by PILRα. Furthermore, we determined the crystal structures of PILRα and its complex with an sTn and its attached peptide region. The structures show that PILRα exhibits large conformational change to recognize simultaneously both the sTn O-glycan and the compact peptide structure constrained by proline residues. Binding and functional assays support this binding mode. These findings provide significant insight into the binding motif and molecular mechanism (which is distinct from sugar-recognition receptors) by which O-glycosylated mucin proteins with sTn modifications are recognized in the immune system as well as during viral entry.
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U2 - 10.1073/pnas.1324105111
DO - 10.1073/pnas.1324105111
M3 - Article
C2 - 24889612
AN - SCOPUS:84902593774
VL - 111
SP - 8877
EP - 8882
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 24
ER -