Structure of human stabilin-1 interacting chitinase-like protein (SI-CLP) reveals a saccharide-binding cleft with lower sugar-binding selectivity.
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.
Meng
Geng
G
National Laboratory of Protein Engineering and Plant Genetic Engineering, Department of Biochemistry and Molecular Biology, College of Life Sciences, Peking University, Beijing 100871, China
Zhao
Yanmei
Y
Bai
Xiaoyun
X
Liu
Yong
Y
Green
Todd J
TJ
Luo
Ming
M
Zheng
Xiaofeng
X
D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D013329:Structure-Activity Relationship
C510246:CHID1 protein, human; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D009844:Oligosaccharides; C012238:chitotetrose