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Title: Recognition of microbial glycans by human intelectin-1

The glycans displayed on mammalian cells can differ markedly from those on microbes. Such differences could, in principle, be 'read' by carbohydrate-binding proteins, or lectins. In this paper, we used glycan microarrays to show that human intelectin-1 (hIntL-1) does not bind known human glycan epitopes but does interact with multiple glycan epitopes found exclusively on microbes: β-linked D-galactofuranose (β-Galf), D-phosphoglycerol–modified glycans, heptoses, D-glycero-D-talo-oct-2-ulosonic acid (KO) and 3-deoxy-D-manno-oct-2-ulosonic acid (KDO). The 1.6-Å-resolution crystal structure of hIntL-1 complexed with β-Galf revealed that hIntL-1 uses a bound calcium ion to coordinate terminal exocyclic 1,2-diols. N-acetylneuraminic acid (Neu5Ac), a sialic acid widespread in human glycans, has an exocyclic 1,2-diol but does not bind hIntL-1, probably owing to unfavorable steric and electronic effects. hIntL-1 marks only Streptococcus pneumoniae serotypes that display surface glycans with terminal 1,2-diol groups. Finally, this ligand selectivity suggests that hIntL-1 functions in microbial surveillance.
Authors:
 [1] ; ORCiD logo [2] ;  [3] ;  [4] ;  [2] ;  [2] ;  [1] ;  [2] ;  [4] ;  [4] ;  [3] ;  [5] ;  [6]
  1. Univ. of Wisconsin, Madison, WI (United States). Dept. of Biochemistry
  2. Univ. of Wisconsin, Madison, WI (United States). Dept. of Chemistry
  3. Scripps Research Inst., La Jolla, CA (United States). Dept. of Cell and Molecular Biology. Dept. of Chemical Physiology
  4. Emory Univ., Atlanta, GA (United States). School of Medicine. Dept. of Biochemistry. Glycomics Center
  5. Univ. of Wisconsin, Madison, WI (United States). Dept. of Bacteriology
  6. Univ. of Wisconsin, Madison, WI (United States). Dept. of Biochemistry. Dept. of Chemistry
Publication Date:
OSTI Identifier:
1214864
Grant/Contract Number:
AC02-06CH11357; R01GM55984; R01AI063596; T32 GM008505; F32 GM100729; GM062116; GM98791; P41GM103694; BIR-9512577; S10 RR13790; P30 CA014520; 1S10RR024715; CHE-9208463; CHE-9629688; 1S10RR08389; 085P1000817
Type:
Accepted Manuscript
Journal Name:
Nature Structural & Molecular Biology
Additional Journal Information:
Journal Volume: 22; Journal Issue: 8; Journal ID: ISSN 1545-9993
Publisher:
Nature Publishing Group
Research Org:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Org:
USDOE; National Inst. of Health (NIH) (United States); National Science Foundation (NSF); Michigan Economic Development Corporation (United States); Michigan Technology Tri-Corridor (United States)
Contributing Orgs:
Scripps Research Inst., La Jolla, CA (United States); Emory Univ., Atlanta, GA (United States)
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES; Carbohydrates