Critical role of amino acid position 343 of surfactant protein-D in the selective binding of glycolipids from Mycobacterium tuberculosis

Tracy K. Carlson, Jordi B. Torrelles, Kelly Smith, Tim Horlacher, Riccardo Castelli, Peter H. Seeberger, Erika C. Crouch, Larry S. Schlesinger

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Surfactant protein D (SP-D), a lectin that recognizes carbohydrates via its C-type carbohydrate recognition domains (CRDs), regulates Mycobacterium tuberculosis (M.tb) -macrophage interactions via recognition of M.tb mannosylated cell wall components. SP-D binds to, agglutinates, and reduces phagocytosis and intracellular growth of M.tb. Species-specific variations in the CRD amino acid sequence contribute to carbohydrate recognition preferences and have been exploited to enhance the antimicrobial properties of SP-D in vitro. Here, we characterized the binding interaction between several wild-type and mutant SP-D neck + CRD trimeric subunits (NCRDs) and pathogenic and nonpathogenic mycobacterial species. Specific amino acid substitutions (i.e., the 343-amino-acid position) that flank the carbohydrate binding groove led to significant increases in binding of only virulent and attenuated M.tb strains and to a lesser extent M. marinum, whereas there was negligible binding to M. avium complex and M. smegmatis. Moreover, a nonconserved mutation at the critical 321-amino-acid position (involved in Ca2+ coordination) abrogated binding to M.tb and M. marinum. We further characterized the binding of NCRDs to the predominant surface-exposed mannosylated lipoglycans of the M.tb cell envelope. Results showed a binding pattern that is dependent on the nature of the side chain of the 343-amino-acid position flanking the SP-D CRD binding groove and the nature of the terminal mannosyl sugar linkages of the mycobacterial lipoglycans. We conclude that the 343 position is critical in defining the binding pattern of SP-D proteins to M.tb and its mannosylated cell envelope components.

Original languageEnglish
Pages (from-to)1473-1484
Number of pages12
JournalGlycobiology
Volume19
Issue number12
DOIs
StatePublished - 2009

Keywords

  • Cell envelope
  • Mannosylated lipoarabinomannan
  • Mycobacterium tuberculosis
  • Pulmonary collectin
  • Surfactant protein D

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