The Crystal Structure of a Novel Mammalian Lectin, Ym1, Suggests a Saccharide Binding Site

Abstract

Ym1, a secretory protein synthesized by activated murine peritoneal macrophages, is a novel mammalian lectin with a binding specificity to GlcN. Lectins are responsible for carbohydrate recognition and for mediating cell-cell and cell-extracellular matrix interactions in microbes, plants, and animals. Glycosaminoglycan heparin/heparan sulfate binding ability was also detected in Ym1. We report here the three-dimensional structure of Ym1 at 2.5-Å resolution by x-ray crystallography. The crystal structure of Ym1 consists of two globular domains, a ␤/␣ triose-phosphate isomerase barrel domain and a small ␣ ؉ ␤ folding domain. A notable electron density of sugar is detected in the Ym1 crystal structure. The saccharide is located inside the triosephosphate isomerase domain at the COOH terminal end of the ␤-strands. Both hydrophilic and hydrophobic interactions are noted in the sugar-binding site in Ym1. Despite the fact that Ym1 is not a chitinase, structurally, Ym1 shares significant homology with chitinase A of Serratia marcescens. Ym1 and chitinase A have a similar carbohydrate binding cleft. This study provides new structure information, which will lead to better understanding of the biological significance of Ym1 and its putative gene members.

Expression of the Ym2 Lectin-binding Protein Is Dependent on Interleukin (IL)-4 and IL-13 Signal Transduction

“…Surface plasmon resonance has demonstrated the binding of Ym1 to GlcN oligomers (chitobiose, chitotriose, and chitotetraose), and heparin sulfate has also been suggested as a candidate ligand (21). Analysis of the crystal structure of Ym1 has also proposed a saccharide-binding site (38). Interestingly, other homologous proteins have been associated with tissue remodeling, a function that may be related to carbohydrate interaction.…”

Differential expression of chitinases identify subsets of murine airway epithelial cells in allergic inflammation

“…Ym1 has been associated with alternatively activated macrophages and has weakly active eosinophil recruiting activity (38,52). Ym1 binds saccharides with a free amine group, including n-glucosamine and their oligosaccharides, as well as heparin, suggesting a role in binding to both extracellular matrix and parasite eggs (8,49). It has therefore been suggested that Ym1 is involved in tissue remodeling involving changes in the extracellular matrix (52).…”

Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide-binding properties

“…These include YKL-40 (chitinase 3-like-1), YKL-39 (chitinase 3-like-2), Ym1/2 (chitinase 3-like-3/4), oviduct-specific glycoprotein and stabilin-1-interacting chitinaselike protein [11][12][13][14][15][16][17]. YKL-40 (also termed HC-gp39 or Chi3l1) was found to be secreted, along with chitotriosidase, from activated human macrophages and it was later detected in the culture supernatant of chondrocytes, synovial cells and osteoblasts [2,11].…”