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Title: Structures of Xenopus Embryonic Epidermal Lectin Reveal a Conserved Mechanism of Microbial Glycan Recognition

Abstract

Intelectins (X-type lectins), broadly distributed throughout chordates, have been implicated in innate immunity. Xenopus laevis embryonic epidermal lectin (XEEL), an intelectin secreted into environmental water by the X. laevis embryo, is postulated to function as a defense against microbes. XEEL is homologous (64% identical) to human intelectin-1 (hIntL-1), which is also implicated in innate immune defense. We showed previously that hIntL-1 binds microbial glycans bearing exocyclic vicinal diol groups. It is unknown whether XEEL has the same ligand specificity. Also unclear is whether XEEL and hIntL-1 have similar quaternary structures, as XEEL lacks the corresponding cysteine residues in hIntL-1 that stabilize the disulfide-linked trimer. These observations prompted us to further characterize XEEL. We found that hIntL-1 and XEEL have similar structural features. Even without the corresponding intermolecular disulfide bonds present in hIntL-1, the carbohydrate recognition domain of XEEL (XEELCRD) forms a stable trimer in solution. The structure of XEELCRD in complex with d-glycerol-1-phosphate, a residue present in microbe-specific glycans, indicated that the exocyclic vicinal diol coordinates to a protein-bound calcium ion. This ligand-binding mode is conserved between XEEL and hIntL-1. The domain architecture of full-length XEEL is reminiscent of a barbell, with two sets of three glycan-binding sites oriented inmore » opposite directions. This orientation is consistent with our observation that XEEL can promote the agglutination of specific serotypes of Streptococcus pneumoniae. Here, these data support a role for XEEL in innate immunity, and they highlight structural and functional conservation of X-type lectins among chordates.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Inst. of Health; National Science Foundation (NSF); USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1770501
Alternate Identifier(s):
OSTI ID: 1254508
Grant/Contract Number:  
AC02–06CH11357; AC02–76SF00515; AC02-06CH11357; AC02-76SF00515; R01GM55984; R01AI063596; T32 GM008505; IOS1353674; DGE-1256259; P41GM103393; BIR-9512577; S10 RR13790
Resource Type:
Journal Article: Published Article
Journal Name:
Journal of Biological Chemistry
Additional Journal Information:
Journal Name: Journal of Biological Chemistry Journal Volume: 291 Journal Issue: 11; Journal ID: ISSN 0021-9258
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; carbohydrate-binding protein; galactofuranose; innate immunity; lectin; protein cross-linking; X-ray crystallography; bacterial agglutination; glycerol phosphate; intelectin; omentin

Citation Formats

Wangkanont, Kittikhun, Wesener, Darryl A., Vidani, Jack A., Kiessling, Laura L., and Forest, Katrina T. Structures of Xenopus Embryonic Epidermal Lectin Reveal a Conserved Mechanism of Microbial Glycan Recognition. United States: N. p., 2016. Web. doi:10.1074/jbc.M115.709212.
Wangkanont, Kittikhun, Wesener, Darryl A., Vidani, Jack A., Kiessling, Laura L., & Forest, Katrina T. Structures of Xenopus Embryonic Epidermal Lectin Reveal a Conserved Mechanism of Microbial Glycan Recognition. United States. https://doi.org/10.1074/jbc.M115.709212
Wangkanont, Kittikhun, Wesener, Darryl A., Vidani, Jack A., Kiessling, Laura L., and Forest, Katrina T. 2016. "Structures of Xenopus Embryonic Epidermal Lectin Reveal a Conserved Mechanism of Microbial Glycan Recognition". United States. https://doi.org/10.1074/jbc.M115.709212.
@article{osti_1770501,
title = {Structures of Xenopus Embryonic Epidermal Lectin Reveal a Conserved Mechanism of Microbial Glycan Recognition},
author = {Wangkanont, Kittikhun and Wesener, Darryl A. and Vidani, Jack A. and Kiessling, Laura L. and Forest, Katrina T.},
abstractNote = {Intelectins (X-type lectins), broadly distributed throughout chordates, have been implicated in innate immunity. Xenopus laevis embryonic epidermal lectin (XEEL), an intelectin secreted into environmental water by the X. laevis embryo, is postulated to function as a defense against microbes. XEEL is homologous (64% identical) to human intelectin-1 (hIntL-1), which is also implicated in innate immune defense. We showed previously that hIntL-1 binds microbial glycans bearing exocyclic vicinal diol groups. It is unknown whether XEEL has the same ligand specificity. Also unclear is whether XEEL and hIntL-1 have similar quaternary structures, as XEEL lacks the corresponding cysteine residues in hIntL-1 that stabilize the disulfide-linked trimer. These observations prompted us to further characterize XEEL. We found that hIntL-1 and XEEL have similar structural features. Even without the corresponding intermolecular disulfide bonds present in hIntL-1, the carbohydrate recognition domain of XEEL (XEELCRD) forms a stable trimer in solution. The structure of XEELCRD in complex with d-glycerol-1-phosphate, a residue present in microbe-specific glycans, indicated that the exocyclic vicinal diol coordinates to a protein-bound calcium ion. This ligand-binding mode is conserved between XEEL and hIntL-1. The domain architecture of full-length XEEL is reminiscent of a barbell, with two sets of three glycan-binding sites oriented in opposite directions. This orientation is consistent with our observation that XEEL can promote the agglutination of specific serotypes of Streptococcus pneumoniae. Here, these data support a role for XEEL in innate immunity, and they highlight structural and functional conservation of X-type lectins among chordates.},
doi = {10.1074/jbc.M115.709212},
url = {https://www.osti.gov/biblio/1770501}, journal = {Journal of Biological Chemistry},
issn = {0021-9258},
number = 11,
volume = 291,
place = {United States},
year = {Tue Mar 01 00:00:00 EST 2016},
month = {Tue Mar 01 00:00:00 EST 2016}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at https://doi.org/10.1074/jbc.M115.709212

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Cited by: 27 works
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Works referenced in this record:

Recognition of microbial glycans by human intelectin-1
journal, July 2015


The X-lectins: A new family with homology to the Xenopus laevis oocyte lectin XL-35
journal, August 2004


Clustal W and Clustal X version 2.0
journal, September 2007


Cloning and expression of a Xenopus laevis oocyte lectin and characterization of its mRNA levels during early development
journal, January 1997


CRYSOL – a Program to Evaluate X-ray Solution Scattering of Biological Macromolecules from Atomic Coordinates
journal, December 1995


Determination of the regularization parameter in indirect-transform methods using perceptual criteria
journal, August 1992


Structural insights into the innate immune recognition specificities of L- and H-ficolins
journal, January 2007


PRIMUS: a Windows PC-based system for small-angle scattering data analysis
journal, September 2003


Domain Interactions in the Fab Fragment: A Comparative Evaluation of the Single-chain Fv and Fab Format Engineered with Variable Domains of Different Stability
journal, April 2005


Lectin from embryos and oocytes of Xenopus laevis. Purification and properties.
journal, July 1982


A unique primary structure, cDNA cloning and function of a galactose-specific lectin from ascidian plasma
journal, March 1999


Assembly of TβRI:TβRII:TGFβ Ternary Complex in vitro with Receptor Extracellular Domains is Cooperative and Isoform-dependent
journal, December 2005


Up-regulation of intelectin in sheep after infection with Teladorsagia circumcincta
journal, March 2008


Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard
journal, May 2009


Advantages of combined transmembrane topology and signal peptide prediction--the Phobius web server
journal, May 2007


Disulfide Bonding in Protein Biophysics
journal, June 2012


Inference of Macromolecular Assemblies from Crystalline State
journal, September 2007


Structural basis for distinct ligand-binding and targeting properties of the receptors DC-SIGN and DC-SIGNR
journal, June 2004


Characterization and comparative analyses of two amphioxus intelectins involved in the innate immune response
journal, May 2013


Potentiometric Analysis of UDP-Galactopyranose Mutase:  Stabilization of the Flavosemiquinone by Substrate
journal, February 2003


PRODRG : a tool for high-throughput crystallography of protein–ligand complexes
journal, July 2004


Human homologs of the Xenopus oocyte cortical granule lectin XL35
journal, January 2001


Crystal structure of the simian immunodeficiency virus (SIV) gp41 core: Conserved helical interactions underlie the broad inhibitory activity of gp41 peptides
journal, August 1998


The lectin-complement pathway - its role in innate immunity and evolution
journal, April 2004


ProteinCCD: enabling the design of protein truncation constructs for expression and crystallization experiments
journal, April 2009


MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009


Comparative genomic and phylogenetic analyses of the intelectin gene family: Implications for their origin and evolution
journal, October 2013


Xenopus galectin-VIIa binds N-glycans of members of the cortical granule lectin family (xCGL and xCGL2)
journal, March 2005


Human Intelectin Is a Novel Soluble Lectin That Recognizes Galactofuranose in Carbohydrate Chains of Bacterial Cell Wall
journal, April 2001


Bacterial lipopolysaccharides stimulate production of XCL1, a calcium-dependent lipopolysaccharide-binding serum lectin, in Xenopus laevis
journal, June 2013


Features and development of Coot
journal, March 2010


New developments in the ATSAS program package for small-angle scattering data analysis
journal, March 2012


Disulfide Bond Acquisition through Eukaryotic Protein Evolution
journal, July 2010


Glycosylation and the Immune System
journal, March 2001


Carbohydrate–Aromatic Interactions in Proteins
journal, November 2015


Capture of heat-killed Mycobacterium bovis bacillus Calmette-Guerin by intelectin-1 deposited on cell surfaces
journal, January 2009


Automatic generation of protein structure cartoons with Pro-origami
journal, October 2011


C OLLECTINS AND F ICOLINS : Humoral Lectins of the Innate Immune Defense
journal, April 2003


ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids
journal, May 2010


Carbohydrate–Aromatic Interactions
journal, June 2012


Genetic Analysis of the Capsular Biosynthetic Locus from All 90 Pneumococcal Serotypes
journal, January 2006


Isolation and characterization of a lectin from the cortical granules of Xenopus laevis eggs
journal, October 1986


Developmental expression of XEEL, a novel molecule of the Xenopus oocyte cortical granule lectin family
journal, July 2003


Phaser crystallographic software
journal, July 2007


Works referencing / citing this record:

Adipose Tissue-Derived Omentin-1 Function and Regulation
reference-book, June 2017