Multimeric and trimeric subunit SP-D are interconvertible structures with distinct ligand interaction

Grith L. Sorensen, Silje V. Hoegh, Rikke Leth-Larsen, Theresa H. Thomsen, Charlotte Floridon, Kelly Smith, Karin Kejling, Ida Tornoe, Erika C. Crouch, Uffe Holmskov

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Surfactant protein-D (SP-D) is a calcium dependent lectin in the innate immune system that facilitates clearance of microbes. The protein is associated with mucosal surfaces, and also found in bronchoalveolar lavage, serum and amniotic fluid. Human SP-D includes trimeric subunits and multimeric assemblies of trimeric subunits, which are stabilized by N-terminal interchain disulfide crosslinks. An N-terminal structural polymorphism (Met11Thr) and associated O-glycosylation are previously shown accompanied by incomplete multimerization and with a relative low proportion of multimeric Thr11 SP-D compared to Met11 SP-D. Multimerization has proven important for enhancement of microbial phagocytosis. In the present study defined multimeric forms of Met11Thr SP-D were isolated from human amniotic fluid. Implementation of ManNAc-affinity chromatography allowed high recovery of natural trimeric SP-D subunits. However, affinity chromatography increased the relative proportion of multimers at the expense of natural trimeric subunits. Multimeric SP-D partially disassembled to form trimeric subunits. The resulting distribution of structural forms was independent of the Met11Thr genotype. Trimeric and multimeric SP-D appeared with distinct patterns of disulphide crosslinking, which partly changed according to interconversion between the structural forms. Solid phase assays demonstrated that trimeric SP-D subunits showed greater binding to LPS and PGN, but lower binding to mannan and LTA, than SP-D multimers. Trimeric SP-D subunits also showed greater binding to endogenous lipoproteins: LDL, oxLDL, and HDL, than multimeric SP-D. In conclusion, purified trimeric and multimeric SP-D represent separate and only partly interconvertible molecular populations with distinct biochemical properties.

Original languageEnglish
Pages (from-to)3060-3069
Number of pages10
JournalMolecular Immunology
Volume46
Issue number15
DOIs
StatePublished - Sep 2009

Keywords

  • HDL
  • LDL
  • Lipopolysaccharide
  • Lipoteichoic acid
  • Mannan
  • Multimers
  • N-acetyl-mannoseamine
  • Peptidoglycan
  • Surfactant protein-D
  • Trimers
  • oxLDL

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