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

Title
Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands
Authors
Fangkun NingChao WangKarin Zemski BerryPitchaimani KandasamyHaolin LiuRobert C. MurphyDennis R. Voelker노주원판철호Shaodong DaiLiwen NiuHong-Wei ChuGongyi Zhang
Keywords
lipid ligand; SPLUNC1; dipalmitoylphosphatidylcholine
Issue Date
2014-12
Publisher
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Citation
VOL 28, NO 12, 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.—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.
URI
http://pubs.kist.re.kr/handle/201004/49208
ISSN
08926638
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE