Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands

Authors
Ning, FangkunWang, ChaoBerry, Karin ZemskiKandasamy, PitchaimaniLiu, HaolinMurphy, Robert C.Voelker, Dennis R.Nho, Chu WonPan, Choel-HoDai, ShaodongNiu, LiwenChu, Hong-WeiZhang, Gongyi
Issue Date
2014-12
Publisher
FEDERATION AMER SOC EXP BIOL
Citation
FASEB JOURNAL, v.28, no.12, pp.5349 - 5360
Abstract
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.
Keywords
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; 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
ISSN
0892-6638
URI
https://pubs.kist.re.kr/handle/201004/126049
DOI
10.1096/fj.14-259291
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KIST Article > 2014
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