Siglec-7 undergoes a major conformational change when complexed with the α(2,8)-disialylganglioside GT1b

Helen Attrill, Akihiro Imamura, Ritu S. Sharma, Makoto Kiso, Paul R. Crocker, Daan M. F. Van Aalten

    Research output: Contribution to journalArticle

    63 Citations (Scopus)

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)32774-32783
    Number of pages10
    JournalJournal of Biological Chemistry
    Volume281
    Issue number43
    DOIs
    Publication statusPublished - 27 Oct 2006

    Fingerprint Dive into the research topics of 'Siglec-7 undergoes a major conformational change when complexed with the α(2,8)-disialylganglioside GT1b'. Together they form a unique fingerprint.

  • Cite this