Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands
- Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands
- Fangkun Ning; Chao Wang; Karin Zemski Berry; Pitchaimani Kandasamy; Haolin Liu; Robert C. Murphy; Dennis R. Voelker; 노주원; 판철호; Shaodong Dai; Liwen Niu; Hong-Wei Chu; Gongyi Zhang
- lipid ligand; SPLUNC1; dipalmitoylphosphatidylcholine
- Issue Date
- The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- VOL 28, NO 12, 5349-5360
- The short palate, lung and nasal epithelial clone 1 (SPLUNC1) protein is a member of the
palate, lung, and nasal epithelium clone (PLUNC) family, also known as bactericidal/permeability-increasing (BPI) fold-containing protein, family A, member 1 (BPIFA1). SPLUNC1 is an abundant protein in human airways, but its function remains poorly understood. The lipid ligands of SPLUNC1 as well as other PLUNC family members are largely unknown, although some
reports provide evidence that lipopolysaccharide (LPS) could be a lipid ligand. Unlike previous hypotheses, we found significant structural differences between SPLUNC1 and BPI. Recombinant SPLUNC1 produced in HEK 293 cells harbored several molecular species of sphingomyelin and phosphatidylcholine as its ligands. Significantly, in vitro lipid-binding studies failed to
demonstrate interactions between SPLUNC1 and LPS, lipoteichoic acid, or polymyxin B. Instead, one of the major and most important pulmonary surfactant phospholipids, dipalmitoylphosphatidylcholine (DPPC), bound to SPLUNC1 with high affinity and specificity. We found that SPLUNC1 could be the first protein receptor for DPPC. These discoveries provide insight into the specific determinants governing the interaction between SPLUNC1 and lipids and also shed light on
novel functions that SPLUNC1 and other PLUNC family members perform in host defense.—Ning, F., Wang, C., Berry, K. Z., Kandasamy, P., Liu, H., Murphy, R. C., Voelker, D. R., Nho, C. W., Pan, C.-H., Dai, S., Niu, L., Chu, H.-W., Zhang, G. Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands.
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