PDBsum entry 2zg3

Immune system/carbohydrate binding prote

PDB id: 2zg3

Contents

Protein chain

210 a.a. *

Ligands

BGC-GAL-SIA

Waters ×34

* Residue conservation analysis

PDB id:

2zg3

Name:

Immune system/carbohydrate binding prote

Title:

Crystal structure of two n-terminal domains of native siglec-5 in complex with 3'-sialyllactose

Structure:

Sialic acid-binding ig-like lectin 5. Chain: a. Fragment: n-terminal v-set and c2-set domain, unp residues 20-233. Synonym: siglec-5, obesity-binding protein 2, ob-binding protein 2, ob-bp2, cd33 antigen-like 2, cd170 antigen. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: siglec5. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

3.00Å R-factor: 0.236 R-free: 0.274

Authors:

M.A.Zhuravleva,P.D.Sun

Key ref:

M.A.Zhuravleva et al. (2008). Structural implications of Siglec-5-mediated sialoglycan recognition. J Mol Biol, 375, 437-447. PubMed id: 18022638 DOI: 10.1016/j.jmb.2007.10.009

Date:

17-Jan-08 Release date: 05-Feb-08

Protein chain

O15389  (SIGL5_HUMAN) -  Sialic acid-binding Ig-like lectin 5 from Homo sapiens

Seq: 551 a.a.

Struc: 210 a.a.

DOI no: 10.1016/j.jmb.2007.10.009

J Mol Biol 375:437-447 (2008)

PubMed id: 18022638

Structural implications of Siglec-5-mediated sialoglycan recognition.

M.A.Zhuravleva, K.Trandem, P.D.Sun.

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.

Selected figure(s)

Figure 4.
Fig. 4. Siglec-5 in complex with (a) α(2,3)-sialyllactose and (b) α(2,6)-sialyllactose. Sections of the unbiased (before the inclusion of the ligand) |F[o]| − |F[c]| electron density maps contoured at 2 σ are shown in the left panels. Siglec-5 is shown in a ribbon diagram (green), with the Arg124 depicted in the balls and sticks. The carbohydrate moieties are in yellow. Interactions between the respective receptor and carbohydrate at the binding site are shown in the right panels. Direct protein–ligand interactions with the Sia and the galactose are shown in red and blue, respectively. Water-mediated interactions are in green. (c) Superposition of the ligand binding sites of the sialoadhesin (gray) and Siglec-5 (green) in their complex structures with α(2,3)-sialyllactose. Residues corresponding to sialoadhesin are given in parentheses.

Figure 5.
Fig. 5. (a) A schematic diagram featuring differences in the G-strand (red) between classic V-set Ig fold (left panel) and Siglec-specific Ig fold (right panel). Sia is shown as a β-strand (green). (b) Schematic representation of conserved main chain interactions between Siglec CFG β-sheet and Sia (green). The mode in which Sia interacts with main chain atoms on the G-strand mimics hydrogen bond interactions (dashed lines) in classic antiparallel pleated β-sheet.

The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2008, 375, 437-447) copyright 2008.

Figures were selected by an automated process.