title: Galectins are human milk glycan receptors.
abstract: The biological recognition of human milk glycans (HMGs) is poorly understood. Because HMGs are rich in galactose we explored whether they might interact with human galectins, which bind galactose-containing glycans and are highly expressed in epithelial cells and other cell types. We screened a number of human galectins for their binding to HMGs on a shotgun glycan microarray consisting of 247 HMGs derived from human milk, as well as to a defined HMG microarray. Recombinant human galectins (hGal)-1, -3, -4, -7, -8 and -9 bound selectively to glycans, with each galectin recognizing a relatively unique binding motif; by contrast hGal-2 did not recognize HMGs, but did bind to the human blood group A Type 2 determinants on other microarrays. Unlike other galectins, hGal-7 preferentially bound to glycans expressing a terminal Type 1 (Galβ1-3GlcNAc) sequence, a motif that had eluded detection on non-HMG glycan microarrays. Interactions with HMGs were confirmed in a solution setting by isothermal titration microcalorimetry and hapten inhibition experiments. These results demonstrate that galectins selectively bind to HMGs and suggest the possibility that galectin-HMG interactions may play a role in infant immunity.
authors.affiliation: Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Noll
authors.affiliation: Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Gourdine
authors.affiliation: Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lasanajak
authors.affiliation: Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Smith
authors.affiliation: Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, CLS 11087-3 Blackfan Circle, Boston, MA 02115, USA rcummin1@bidmc.harvard.edu.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cummings
mesh_terms: D001665:Binding Sites; D002240:Carbohydrate Sequence; D005260:Female; D005690:Galactose / Q000737:chemistry; D037161:Galectins / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D046228:Microarray Analysis; D008895:Milk, Human / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification
chemical_list: D037161:Galectins; D011134:Polysaccharides; D011994:Recombinant Proteins; D005690:Galactose
keywords: galectins; glycan microarrays; glycan recognition; human milk glycans; shotgun glycomics