title: Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands.
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.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, China; Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado, USA;
authors.forename: Fangkun
authors.initials: F
authors.lastname: Ning
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado, USA;
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, University of Colorado Denver, Aurora, Colorado, USA;
authors.forename: Karin Zemski
authors.initials: KZ
authors.lastname: Berry
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, USA; and.
authors.forename: Pitchaimani
authors.initials: P
authors.lastname: Kandasamy
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado, USA;
authors.forename: Haolin
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, University of Colorado Denver, Aurora, Colorado, USA;
authors.forename: Robert C
authors.initials: RC
authors.lastname: Murphy
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, USA; and.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
authors.affiliation: Functional Food Center, Korea Institute of Science and Technology, GangNeung, Korea.
authors.forename: Chu Won
authors.initials: CW
authors.lastname: Nho
authors.affiliation: Functional Food Center, Korea Institute of Science and Technology, GangNeung, Korea.
authors.forename: Choel-Ho
authors.initials: CH
authors.lastname: Pan
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado, USA;
authors.forename: Shaodong
authors.initials: S
authors.lastname: Dai
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, China; lwniu@ustc.edu.cn chuh@njhealth.org.
authors.forename: Liwen
authors.initials: L
authors.lastname: Niu
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado, USA; Department of Medicine, National Jewish Health, Denver, Colorado, USA; and lwniu@ustc.edu.cn chuh@njhealth.org.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Chu
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado, USA;
authors.forename: Gongyi
authors.initials: G
authors.lastname: Zhang
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D008024:Ligands; D008055:Lipids / Q000737:chemistry*; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
chemical_list: C485599:BPIFA1 protein, human; D017931:DNA Primers; D006023:Glycoproteins; D008024:Ligands; D008055:Lipids; D010750:Phosphoproteins
keywords: DPPC; SM; lipid ligand