3BXW

Crystal Structure of Stabilin-1 Interacting Chitinase-Like Protein, SI-CLP

Summary for 3BXW

• Entry DOI: 10.2210/pdb3bxw/pdb
• Descriptor: Chitinase domain-containing protein 1, SULFATE ION (3 entities in total)
• Functional Keywords: tim barrel, lysosome, secreted, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: Q9BWS9
• Total number of polymer chains: 2
• Total formula weight: 90203.27

Authors

Meng, G.,Green, T.J. (deposition date: 2008-01-15, release date: 2009-01-20, Last modification date: 2024-03-13)

Primary citation

Meng, G.,Zhao, Y.,Bai, X.,Liu, Y.,Green, T.J.,Luo, M.,Zheng, X.
Structure of human stabilin-1 interacting chitinase-like protein (SI-CLP) reveals a saccharide-binding cleft with lower sugar-binding selectivity.
J.Biol.Chem., 285:39898-39904, 2010

PubMed Abstract: Human secreted protein stabilin-1 interacting chitinase-like protein (SI-CLP) has been identified as a novel member of Glyco_18 domain-containing proteins that is involved in host defense and inflammatory reactions. Efficient secretion of SI-CLP is mediated by its interaction with the endocytic/sorting receptor stabilin-1. SI-CLP is expressed abundantly in macrophages and neutrophils and is up-regulated by Th2 cytokine IL-4 and glucocorticoid, which suggest that SI-CLP could be a marker for adverse effects of glucocorticoid therapy. To gain insight into the biological function of SI-CLP, we determined the crystal structure of SI-CLP at 2.7 Å resolution by x-ray crystallography and found that it featured a typical triose-phosphate isomerase barrel fold with a putative saccharide-binding cleft. Comparison with other chitinase-like proteins showed the cleft to be atypically wide and open. The saccharide-binding capacity of SI-CLP was investigated, and its ligand-binding specificity was found to relate to the length of the oligosaccharides, with preference for chitotetraose. Further investigations reveal that SI-CLP could bind LPS in vitro and neutralize its endotoxin effect on macrophages. Our results demonstrate the saccharide-binding property of SI-CLP by structure and in vitro biochemical analyses and suggest the possible roles of SI-CLP in pathogen sensing and endotoxin neutralization.

PubMed: 20724479
DOI: 10.1074/jbc.M110.130781

Experimental method

X-RAY DIFFRACTION (2.7 Å)