Structural Implications of Siglec-5-Mediated Sialoglycan Recognition

Marina A. Zhuravleva, Kathryn Trandem, Peter D. Sun
<span title="">2008</span> <i title="Elsevier BV"> <a target="_blank" rel="noopener" href="" style="color: black;">Journal of Molecular Biology</a> </i> &nbsp;
Sialic acid Ig-like binding lectins are important mediators of recognition and signaling events among myeloid cells. To investigate the molecular mechanism underlying Siglec functions, we have determined the crystal structure of the two N-terminal extracellular domains of a 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
more &raquo; ... sulfide bond. The α(2,3)-sialyllactose and α(2,6)-sialyllactose complexed structures showed a conserved sialic acid recognition motif that involves both Arg 124 and a portion of the Gstrand in the V-set domain forming β-sheet-like hydrogen bonds with the glycerol side chain of the sialic acid. Only few direct protein contacts to the sub-terminal 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 the linkage-dependent Siglec carbohydrate recognition and suggest that Siglec-5 and other CD33-related Siglec receptors are more promiscuous in sialo-glycan recognition than previously understood.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="">doi:10.1016/j.jmb.2007.10.009</a> <a target="_blank" rel="external noopener" href="">pmid:18022638</a> <a target="_blank" rel="external noopener" href="">pmcid:PMC2245879</a> <a target="_blank" rel="external noopener" href="">fatcat:vlh5jcmh6jchpp2tqnvo2xu2xq</a> </span>
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