2. Academic Validation
  3. 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

  • FASEB J. 2014 Dec;28(12):5349-60. doi: 10.1096/fj.14-259291.
Fangkun Ning 1,  Chao Wang 2,  Karin Zemski Berry 3,  Pitchaimani Kandasamy 4,  Haolin Liu 2,  Robert C Murphy 3,  Dennis R Voelker 4,  Chu Won Nho 5,  Choel-Ho Pan 5,  Shaodong Dai 2,  Liwen Niu 6,  Hong-Wei Chu 7,  Gongyi Zhang 2
Affiliations

Affiliations

  • 1 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;
  • 2 Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado, USA;
  • 3 Department of Pharmacology, University of Colorado Denver, Aurora, Colorado, USA;
  • 4 Department of Medicine, National Jewish Health, Denver, Colorado, USA; and.
  • 5 Functional Food Center, Korea Institute of Science and Technology, GangNeung, Korea.
  • 6 School of Life Sciences, University of Science and Technology of China, Hefei, China; [email protected] [email protected].
  • 7 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 [email protected] [email protected].
PMID: 25223608 DOI: 10.1096/fj.14-259291
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

DPPC; SM; lipid ligand.

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