Crystal Structure of the Eosinophil Major Basic Protein at 1.8 Å

The eosinophil major basic protein (EMBP) is the predominant constituent of the crystalline core of the eosinophil primary granule. EMBP is directly implicated in epithelial cell damage, exfoliation, and bronchospasm in allergic diseases such as asthma. Here we report the crystal structure of EMBP at 1.8 Å resolution, and show that it is similar to that of members of the C-type lectin superfamily with which it shares minimal amino acid sequence identity (∼15–28%). However, this protein lacks a Ca2+/carbohydrate-binding site. Our analysis suggests that EMBP specifically binds heparin. Based on our results, we propose a possible new function for this protein, which is likely to have implications for EMBP function.

• Publication year

  2001

• Venue

  Journal of Biological Chemistry

• Publication date

  2001-07-13

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.M100848200PMID 11319227
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The effect of purified human eosinophil major basic protein on mammalian ciliary activity.

  2015cited by this paper
• Crystal Structure of the C-type Lectin-like Domain from the Human Hematopoietic Cell Receptor CD69*

  2001cited by this paper
• Crystal structure of human CD69: a C-type lectin-like activation marker of hematopoietic cells.

  2000cited by this paper
• Mechanisms of eosinophil-associated inflammation.

  2000cited by this paper
• Expression of Recombinant Human Pregnancy-associated Plasma Protein-A and Identification of the Proform of Eosinophil Major Basic Protein as Its Physiological Inhibitor*

  2000cited by this paper
• A Novel and Highly Divergent Homolog of Human Eosinophil Granule Major Basic Protein*

  1999cited by this paper
• Structure of CD94 reveals a novel C-type lectin fold: implications for the NK cell-associated CD94/NKG2 receptors.

  1999cited by this paper
• Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand

  1999cited by this paper
• The structure of a tunicate C-type lectin from Polyandrocarpa misakiensis complexed with D -galactose.

  1999cited by this paper
• The structure and function of a foot‐and‐mouth disease virus–oligosaccharide receptor complex

  1999cited by this paper
• Crystal structure of the trimeric alpha-helical coiled-coil and the three lectin domains of human lung surfactant protein D.

  1999cited by this paper
• Structure of the C-type lectin carbohydrate recognition domain of human tetranectin.

  1998cited by this paper
• The C‐type lectin superfamily in the immune system

  1998cited by this paper
• Mechanism of N-Acetylgalactosamine Binding to a C-type Animal Lectin Carbohydrate-recognition Domain*

  1998cited by this paper
• Regulation and processing of a precursor form of eosinophil granule major basic protein (ProMBP) in differentiating eosinophils.

  1998cited by this paper
• Crystallography & NMR system: A new software suite for macromolecular structure determination.

  1998cited by this paper
• The solution structure of type II antifreeze protein reveals a new member of the lectin family.

  1998cited by this paper
• Evolving views of protein glycosylation.

  1998cited by this paper
• Macromolecular crystal annealing: overcoming increased mosaicity associated with cryocrystallography.

  1998cited by this paper
• [20] Processing of X-ray diffraction data collected in oscillation mode.

  1997cited by this paper
• Processing of X-ray diffraction data collected in oscillation mode.

  1997cited by this paper
• Crystal structure of human lithostathine, the pancreatic inhibitor of stone formation.

  1996cited by this paper
• Structural Analysis of Monosaccharide Recognition by Rat Liver Mannose-binding Protein (*)

  1996cited by this paper
• Eosinophil-fibroblast interactions. Granule major basic protein interacts with IL-1 and transforming growth factor-beta in the stimulation of lung fibroblast IL-6-type cytokine production.

  1996cited by this paper
• Protein fold recognition using sequence‐derived predictions

  1996cited by this paper
• Expression, purification, and characterization of the recombinant proform of eosinophil granule major basic protein.

  1995cited by this paper
• NMRPipe: A multidimensional spectral processing system based on UNIX pipes

  1995cited by this paper
• Insight into E-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/EGF domains

  1994cited by this paper
• Localization of disulfide bridges and free sulfhydryl groups in human eosinophil granule major basic protein

  1994cited by this paper
• Human mannose-binding protein carbohydrate recognition domain trimerizes through a triple α-helical coiled-coil

  1994cited by this paper
• Location and nature of carbohydrate groups in proform of human major basic protein isolated from pregnancy serum.

  1994cited by this paper
• Recognition of complex carbohydrates by Ca(2+)-dependent animal lectins.

  1993cited by this paper
• ALSCRIPT: a tool to format multiple sequence alignments.

  1993cited by this paper
• Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor.

  1993cited by this paper
• Biology of animal lectins.

  1993cited by this paper
• The biology of the eosinophilic leukocyte.

  1993cited by this paper
• Structure of a C-type mannose-binding protein complexed with an oligosaccharide

  1992cited by this paper
• Eosinophil activation and function in health and disease.

  1992cited by this paper
• Eosinophil granule proteins in peripheral blood granulocytes

  1992cited by this paper
• Interaction of eosinophil granule major basic protein with synthetic lipid bilayers: A mechanism for toxicity

  1992cited by this paper
• Engineering galactose-binding activity into a C-type mannose-binding protein

  1992cited by this paper
• A program to produce both detailed and schematic plots of protein structures

  1991cited by this paper
• Structure of the calcium-dependent lectin domain from a rat mannose-binding protein determined by MAD phasing.

  1991cited by this paper
• Acidic polyamino acids inhibit human eosinophil granule major basic protein toxicity. Evidence of a functional role for ProMBP.

  1991cited by this paper
• Protein folding and association: Insights from the interfacial and thermodynamic properties of hydrocarbons

  1991cited by this paper
• Human eosinophil major basic protein induces airway constriction and airway hyperresponsiveness in primates.

  1991cited by this paper
• In vitro killing of microfilariae of Brugia pahangi and Brugia malayi by eosinophil granule proteins.

  1990cited by this paper
• Noncytotoxic activation of neutrophils by eosinophil granule major basic protein. Effect on superoxide anion generation and lysosomal enzyme release.

  1990cited by this paper
• Homology of cytotoxic protein of eosinophilic leukocytes with IgE receptor Fc epsilon RII: implications for its structure and function.

  1989cited by this paper
• Homology of cytotoxic protein of eosinophilic leukocytes with IgE receptor Fcϵ RII: Implications for its structure and function

  1989cited by this paper
• Acidic precursor revealed in human eosinophil granule major basic protein cDNA [published erratum appears in J Exp Med 1989 Sep 1;170(3):1057]

  1988cited by this paper
• Two distinct classes of carbohydrate-recognition domains in animal lectins.

  1988cited by this paper
• Isolation of a complementary DNA clone encoding a precursor to human eosinophil major basic protein

  1988cited by this paper
• Effect of human eosinophil major basic protein on ion transport in dog tracheal epithelium.

  1988cited by this paper
• Human eosinophil major basic protein causes hyperreactivity of respiratory smooth muscle. Role of the epithelium.

  1988cited by this paper
• Comparative toxicity of purified human eosinophil granule proteins for newborn larvae of Trichinella spiralis.

  1987cited by this paper
• Localization of human eosinophil granule major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin by immunoelectron microscopy.

  1986cited by this paper
• Activation of basophil and mast cell histamine release by eosinophil granule major basic protein

  1983cited by this paper
• Elevated serum levels of the eosinophil granule major basic protein in patients with eosinophilia.

  1981cited by this paper
• Damage to schistosomula of Schistosoma mansoni induced directly by eosinophil major basic protein.

  1979cited by this paper
• Cytotoxic properties of the eosinophil major basic protein.

  1979cited by this paper
• Comparative properties of the Charcot-Leyden crystal protein and the major basic protein from human eosinophils.

  1976cited by this paper
• PHYSIOCHEMICAL AND BIOLOGICAL PROPERTIES OF THE MAJOR BASIC PROTEIN FROM GUINEA PIG EOSINOPHIL GRANULES

  1974cited by this paper

• The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue‐Specific Perspectives

  2025cites this paper
• In situ crystalline structure of the human eosinophil major basic protein-1

  2024cites this paper
• Structural insights into the covalent regulation of PAPP-A activity by proMBP and STC2

  2022cites this paper
• The correlation between proteoglycan 2 and neuropsychiatric systemic lupus erythematosus.

  2022cites this paper
• GWAS of genetic factors affecting white blood cell morphological parameters in Sardinians uncovers influence of chromosome 11 innate immunity gene cluster on eosinophil morphology.

  2022cites this paper
• Therapeutic Potential of MRGPRX2 Inhibitors on Mast Cells

  2021cites this paper
• Hypereosinophilia as a Cause of Recurrent Stroke

  2020cites this paper
• Oral Administration of 99mTechnetium-Labeled Heparin in Eosinophilic Esophagitis.

  2020cites this paper
• Functional Mammalian Amyloids and Amyloid-Like Proteins

  2020influential citation
• Bioinformatic analysis of eosinophil activity and its implications for model and target species

  2019cites this paper
• Charcot-Leyden crystal protein/galectin-10 is a surrogate biomarker of eosinophilic airway inflammation in asthma.

  2019cites this paper
• Peptides of major basic protein and eosinophil cationic protein activate human mast cells

  2019cites this paper
• The significance of eosinophils in predicting the severity of acute ischemic stroke

  2017cites this paper
• Pharmacology of Heparin and Related Drugs

  2016cites this paper
• Rapid Evolution of Primate Type 2 Immune Response Factors Linked to Asthma Susceptibility

  2016cites this paper
• Toxicity of eosinophil MBP is repressed by intracellular crystallization and promoted by extracellular aggregation.

  2015cites this paper
• Structural and Computational Glycobiology: Immunity and Infection

  2015cites this paper
• Computational and Experimental Prediction of Human C-Type Lectin Receptor Druggability

  2014cites this paper
• Docking Server for the Identification of Heparin Binding Sites on Proteins

  2014cites this paper
• Eosinophil Granule Proteins: Form and Function

  2014cites this paper
• Eosinophil major basic protein activates human cord blood mast cells primed with fibroblast membranes by integrin‐β1

  2013cites this paper
• The oesophageal string test: a novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis

  2012cites this paper
• Antimicrobial activity of human eosinophil granule proteins: involvement in host defence against pathogens

  2012cites this paper
• Lectins: An Overview

  2012cites this paper
• C-Type Lectins Family

  2012cites this paper
• Les polyèdres viraux : armures cristallines des virus d'insectes.

  2012cites this paper
• Emerging Groups of C-Type Lectins

  2012cites this paper
• Eosinophils: multifaceted biological properties and roles in health and disease

  2011cites this paper
• Placental Regulation of Peptide Hormone and Growth Factor Activity by proMBP1

  2011influential citation
• Eosinophil Ribonucleases and Their Cutaneous Lesion-Forming Activity1

  2009cites this paper
• B M ] 3 O ct 2 00 5 Protein crystallization in vivo

  2008cites this paper
• Human Eosinophil Major Basic Protein 2: Location of Disulfide Bonds and Free Sulfhydryl Groups

  2007cites this paper
• The three-dimensional structure of codakine and related marine C-type lectins.

  2007cites this paper
• The role of the complement anaphylatoxins in the recruitment of eosinophils.

  2007cites this paper
• Cell Surface Detachment of Pregnancy-associated Plasma Protein-A Requires the Formation of Intermolecular Proteinase-Inhibitor Disulfide Bonds and Glycosaminoglycan Covalently Bound to the Inhibitor*

  2007cites this paper
• Characterization of a recombinant C-type lectin, rCEL-IV, expressed in Escherichia coli cells using a synthetic gene.

  2006cites this paper
• The Proform of the Eosinophil Major Basic Protein Binds the Cell Surface through a Site Distinct from Its C-type Lectin Ligand-binding Region*

  2006cites this paper
• Proteinase Inhibition by Proform of Eosinophil Major Basic Protein (pro-MBP) Is a Multistep Process of Intra- and Intermolecular Disulfide Rearrangements*

  2005cites this paper
• Protein crystallization in vivo

  2005cites this paper
• Eosinophil-granule major basic protein, a C-type lectin, binds heparin.

  2005cites this paper
• The C‐type lectin‐like domain superfamily

  2005cites this paper
• In silico analysis of C-type lectin domains’ structure and properties

  2004cites this paper
• Inhibition of proteolysis by the proform of eosinophil major basic protein (proMBP) requires covalent binding to its target proteinase

  2004cites this paper
• Characteristic Recognition of N-Acetylgalactosamine by an Invertebrate C-type Lectin, CEL-I, Revealed by X-ray Crystallographic Analysis*

  2004cites this paper
• The Link Module from Ovulation- and Inflammation-associated Protein TSG-6 Changes Conformation on Hyaluronan Binding*

  2003cites this paper
• Effects of human mast cell tryptase and eosinophil granule proteins on the kinetics of blood clotting

  2003cites this paper
• Comparative analysis of structural properties of the C‐type‐lectin‐like domain (CTLD)

  2003cites this paper
• Complex of Pregnancy-associated Plasma Protein-A and the Proform of Eosinophil Major Basic Protein

  2003cites this paper
• Interactions of eosinophil granule proteins with skin: limits of detection, persistence, and vasopermeabilization.

  2003cites this paper
• Amino Acid Sequence and Carbohydrate-binding Analysis of the N-acetyl-D-galactosamine-specific C-Type Lectin, CEL-I, from the Holothuroidea, Cucumaria echinata

  2002cites this paper
• Binding of Sucrose Octasulphate to the C‐Type Lectin‐Like Domain of the Recombinant Natural Killer Cell Receptor NKR‐P1A Observed by NMR Spectroscopy

  2002cites this paper
• Principles of structures of animal and plant lectins.

  2002cites this paper
• Peptide-based analysis of amino acid sequences important to the biological activity of eosinophil granule major basic protein.

  2001cites this paper
• New structural insights into lectin-type proteins of the immune system.

  2001cites this paper
• Nitric Oxide Increases Leukocyte Granule Release During Simulated Extracorporeal Circulation1

  2000cites this paper