2HRL

Siglec-7 in complex with GT1b

Summary for 2HRL

• Entry DOI: 10.2210/pdb2hrl/pdb
• Related: 1O7S 1O7V 2DF3 2G5R
• Descriptor: Sialic acid-binding Ig-like lectin 7, N-acetyl-alpha-neuraminic acid-(2-8)-N-acetyl-alpha-neuraminic acid-(2-3)-[2-acetamido-2-deoxy-beta-D-galactopyranose-(1-4)]beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: ig-like domain, siglec, ganglioside, siglec-7, cell adhesion
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: Q9Y286
• Total number of polymer chains: 1
• Total formula weight: 16106.75

Authors

Attrill, H.,Imamura, A.,Sharma, R.S.,Kiso, M.,Crocker, P.R.,van Aalten, D.M.F. (deposition date: 2006-07-20, release date: 2006-08-15, Last modification date: 2024-10-30)

Primary citation

Attrill, H.,Imamura, A.,Sharma, R.S.,Kiso, M.,Crocker, P.R.,van Aalten, D.M.F.
Siglec-7 Undergoes a Major Conformational Change When Complexed with the {alpha}(2,8)-Disialylganglioside GT1b
J.Biol.Chem., 281:32774-32783, 2006

PubMed 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 alpha(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 alpha(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.

PubMed: 16895906
DOI: 10.1074/jbc.M601714200

Experimental method

X-RAY DIFFRACTION (1.85 Å)