Contributions of phenylalanine 335 to ligand recognition by human surfactant protein D: ring interactions with SP-D ligands

The Journal of Biological Chemistry
E CrouchJames Head

Abstract

Surfactant protein D (SP-D) is an innate immune effector that contributes to antimicrobial host defense and immune regulation. Interactions of SP-D with microorganisms and organic antigens involve binding of glycoconjugates to the C-type lectin carbohydrate recognition domain (CRD). A trimeric fusion protein encoding the human neck+CRD bound to the aromatic glycoside p-nitrophenyl-alpha-D-maltoside with nearly a log-fold higher affinity than maltose, the prototypical competitor. Maltotriose, which has the same linkage pattern as the maltoside, bound with intermediate affinity. Site-directed substitution of leucine for phenylalanine 335 (Phe-335) decreased affinities for the maltoside and maltotriose without significantly altering the affinity for maltose or glucose, and substitution of tyrosine or tryptophan for leucine restored preferential binding to maltotriose and the maltoside. A mutant with alanine at this position failed to bind to mannan or maltose-substituted solid supports. Crystallographic analysis of the human neck+CRD complexed with maltotriose or p-nitrophenyl-maltoside showed stacking of the terminal glucose or nitrophenyl ring with the aromatic ring of Phe-335. Our studies indicate that Phe-335, which is evoluti...Continue Reading

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Citations

Mar 17, 2010·The Journal of Biological Chemistry·Erika C CrouchAzzaq Belaaouaj
Jun 12, 2012·The Journal of Biological Chemistry·Martin van EijkBarbara A Seaton
Oct 24, 2012·Glycobiology·Diego F GautoMarcelo A Martí
Jan 8, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sadis MatalonErika C Crouch
Jan 8, 2010·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Zissis C ChroneosVirginia L Shepherd
Feb 10, 2010·Medical Mycology·Scarlett Geunes-BoyerWilliam J Steinbach
Aug 12, 2010·Journal of Nucleic Acids·Frédéric RosuEdwin De Pauw
Apr 18, 2016·Molecular Aspects of Medicine·Ian LokeMorten Thaysen-Andersen
Jun 29, 2016·Journal of Structural Biology·Anika ReinhardtPeter H Seeberger
Apr 29, 2010·Innate Immunity·Barbara A SeatonRichard Mendelsohn
Jul 6, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Kevan L HartshornErika C Crouch
Apr 8, 2014·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nikolaos M NikolaidisKevan L Hartshorn
Nov 20, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mitchell WhiteKevan Hartshorn
Oct 20, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Soren HansenUffe Holmskov

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