2ZG1

Crystal Structure of Two N-terminal Domains of Siglec-5 in Complex with 6'-Sialyllactose

Summary for 2ZG1

• Entry DOI: 10.2210/pdb2zg1/pdb
• Related: 1O7S 1QFO 2ZG2 2ZG3
• Descriptor: Sialic acid-binding Ig-like lectin 5, N-acetyl-alpha-neuraminic acid (3 entities in total)
• Functional Keywords: siglec-5 inhibitory receptor, two-domain structure, v-set, c2-set, ig-like domain, sialic acid, 6'-sialyllactose complex, cell adhesion, glycoprotein, immunoglobulin domain, lectin, membrane, polymorphism, transmembrane, immune system-carbohydrate binding protein complex, immune system/carbohydrate binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: O15389
• Total number of polymer chains: 1
• Total formula weight: 24641.62

Authors

Zhuravleva, M.A.,Sun, P.D. (deposition date: 2008-01-17, release date: 2008-02-05, Last modification date: 2024-10-30)

Primary citation

Zhuravleva, M.A.,Trandem, K.,Sun, P.D.
Structural implications of Siglec-5-mediated sialoglycan recognition
J.Mol.Biol., 375:437-447, 2008

PubMed Abstract: Sialic acid (Sia) Ig-like binding lectins are important mediators of recognition and signaling events among myeloid cells. To investigate the molecular mechanism underlying sialic acid Ig-like lectin (Siglec) functions, we determined the crystal structure of the two N-terminal extracellular domains of human myeloid cell inhibitory receptor Siglec-5 (CD170) and its complexes with two sialylated carbohydrates. The native structure revealed an unusual conformation of the CC' ligand specificity loop and a unique interdomain disulfide bond. The alpha(2,3)- and alpha(2,6)-sialyllactose complexed structures showed a conserved Sia recognition motif that involves both Arg124 and a portion of the G-strand in the V-set domain forming beta-sheet-like hydrogen bonds with the glycerol side chain of the Sia. Only few protein contacts to the subterminal sugars are observed and mediated by the highly variable GG' linker and CC' loop. These structural observations, in conjunction with surface plasmon resonance binding assays, provide mechanistic insights into linkage-dependent Siglec carbohydrate recognition and suggest that Siglec-5 and other CD33-related Siglec receptors are more promiscuous in sialoglycan recognition than previously understood.

PubMed: 18022638
DOI: 10.1016/j.jmb.2007.10.009

Experimental method

X-RAY DIFFRACTION (2.7 Å)