TY - JOUR
T1 - Siglec-7 undergoes a major conformational change when complexed with the α(2,8)-disialylganglioside GT1b
AU - Attrill, Helen
AU - Imamura, Akihiro
AU - Sharma, Ritu S.
AU - Kiso, Makoto
AU - Crocker, Paul R.
AU - Van Aalten, Daan M. F.
N1 - MEDLINE® is the source for the MeSH terms of this document.
PY - 2006/10/27
Y1 - 2006/10/27
N2 - The siglecs are a group of mammalian sialic acid binding receptors expressed predominantly in the immune system. The CD33-related siglecs show complex recognition patterns for sialylated glycans. Siglec-7 shows a preference for a(2,8)-disialylated ligands and provides a structural template for studying the key interactions that drive this selectivity. We have co-crystallized Siglec-7 with a synthetic oligosaccharide corresponding to the a(2,8)-disialylated ganglioside GT1b. The crystal structure of the complex offers a first glimpse into how this important family of lectins binds the structurally diverse gangliosides. The structure reveals that the C-C' loop, a region implicated in previous studies as driving siglec specificity, undergoes a dramatic conformational shift, allowing it to interact with the underlying neutral glycan core of the ganglioside. The structural data in combination with mutagenesis studies show that binding of the ganglioside is driven by extensive hydrophobic contacts together with key polar interactions and that the binding site structure is complementary to preferred solution conformations of GT1b.
AB - The siglecs are a group of mammalian sialic acid binding receptors expressed predominantly in the immune system. The CD33-related siglecs show complex recognition patterns for sialylated glycans. Siglec-7 shows a preference for a(2,8)-disialylated ligands and provides a structural template for studying the key interactions that drive this selectivity. We have co-crystallized Siglec-7 with a synthetic oligosaccharide corresponding to the a(2,8)-disialylated ganglioside GT1b. The crystal structure of the complex offers a first glimpse into how this important family of lectins binds the structurally diverse gangliosides. The structure reveals that the C-C' loop, a region implicated in previous studies as driving siglec specificity, undergoes a dramatic conformational shift, allowing it to interact with the underlying neutral glycan core of the ganglioside. The structural data in combination with mutagenesis studies show that binding of the ganglioside is driven by extensive hydrophobic contacts together with key polar interactions and that the binding site structure is complementary to preferred solution conformations of GT1b.
UR - http://www.scopus.com/inward/record.url?scp=33845948942&partnerID=8YFLogxK
U2 - 10.1074/jbc.M601714200
DO - 10.1074/jbc.M601714200
M3 - Article
AN - SCOPUS:33845948942
SN - 0021-9258
VL - 281
SP - 32774
EP - 32783
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 43
ER -