Ning, Fangkun Wang, Chao Berry, Karin Zemski Kandasamy, Pitchaimani Liu, Haolin Murphy, Robert C. Voelker, Dennis R. Nho, Chu Won Pan, Choel-Ho Dai, Shaodong Niu, Liwen Chu, Hong-Wei Zhang, Gongyi 2024-01-20T08:04:54Z 2024-01-20T08:04:54Z 2021-09-02 2014-12 0892-6638 https://pubs.kist.re.kr/handle/201004/126049 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. English FEDERATION AMER SOC EXP BIOL BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN PSEUDOMONAS-AERUGINOSA INFECTION BINDS MYCOPLASMA-PNEUMONIAE CYSTIC-FIBROSIS AIRWAYS GRAM-NEGATIVE BACTERIA SURFACTANT-PROTEIN CRYSTAL-STRUCTURE MASS-SPECTROMETRY HIGH-AFFINITY HOST-DEFENSE Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands Article 10.1096/fj.14-259291 1 FASEB JOURNAL, v.28, no.12, pp.5349 - 5360 FASEB JOURNAL 28 12 5349 5360 scie scopus 000345894500028 2-s2.0-84919807964 Biochemistry & Molecular Biology Biology Cell Biology Biochemistry & Molecular Biology Life Sciences & Biomedicine - Other Topics Cell Biology Article BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN PSEUDOMONAS-AERUGINOSA INFECTION BINDS MYCOPLASMA-PNEUMONIAE CYSTIC-FIBROSIS AIRWAYS GRAM-NEGATIVE BACTERIA SURFACTANT-PROTEIN CRYSTAL-STRUCTURE MASS-SPECTROMETRY HIGH-AFFINITY HOST-DEFENSE lipid ligand SM DPPC