PDBsum entry 1h8u

Lectin

PDB id: 1h8u

Contents

Protein chains

115 a.a. *

Ligands

SO4 ×8

GOL ×2

Waters ×158

* Residue conservation analysis

PDB id:

1h8u

Name:

Lectin

Title:

Crystal structure of the eosinophil major basic protein at 1.8a: an atypical lectin with a paradigm shift in specificity

Structure:

Eosinophil granule major basic protein 1. Chain: a, b. Synonym: mbp

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: blood. Cell: eosinophil. Organelle: primary granule. Cellular_location: secretory granules

Resolution:

1.80Å R-factor: 0.234 R-free: 0.264

Authors:

G.J.Swaminathan,A.J.Weaver,D.A.Loegering,J.L.Checkel,D.D.Leonidas, G.J.Gleich,K.R.Acharya

Key ref:

G.J.Swaminathan et al. (2001). Crystal structure of the eosinophil major basic protein at 1.8 A. An atypical lectin with a paradigm shift in specificity. J Biol Chem, 276, 26197-26203. PubMed id: 11319227 DOI: 10.1074/jbc.M100848200

Date:

15-Feb-01 Release date: 17-Jul-01

Protein chains

P13727  (PRG2_HUMAN) -  Bone marrow proteoglycan from Homo sapiens

Seq: 222 a.a.

Struc: 115 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1074/jbc.M100848200

J Biol Chem 276:26197-26203 (2001)

PubMed id: 11319227

Crystal structure of the eosinophil major basic protein at 1.8 A. An atypical lectin with a paradigm shift in specificity.

G.J.Swaminathan, A.J.Weaver, D.A.Loegering, J.L.Checkel, D.D.Leonidas, G.J.Gleich, K.R.Acharya.

ABSTRACT

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 A 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 (approximately 15--28%). However, this protein lacks a Ca(2+)/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.

Selected figure(s)

Figure 1.
Fig. 1. a, structure of the EMBP dimer with bound sulfate ions. The bound ions are proposed to form a putative carbohydrate-binding site as defined in the case of C-TLs. The sulfate ions and disulfide bridges are shown in ball-and-stick representation, helices are shown in red, whereas the -strands are shown in olive green. b, stereoview representation comparing EMBP (black) with the C-TL domains of lithostathine (blue), human mannose-binding protein (red), human lung surfactant protein (magenta), and E-selectin (green). EMBP has overall topology similar to that of lectin domains of other C-TL proteins. The region corresponding to the carbohydrate-binding site is different in EMBP. The C-TL carbohydrate-binding site is shown by the position of -methyl-D-galactoside (ball-and-stick) and calcium ion (blue sphere) from the structure of rat mannose-binding protein (PDB Code: 1AFA). c, structural comparison of EMBP with other representative C-TL domain-containing proteins (see Refs. 30, 32-38, 56, 57). Calcium ions are shown as blue spheres. In tunicate lectin TC-14 (58), the magenta sphere represents a bound zinc ion. All figures generated with the program MOLSCRIPT (59). d, the nature of the carbohydrate-binding site revealed by sequence comparisons between EMBP and other C-TLs. Invariant residues involved in carbohydrate interactions are shown in white on a black background. Other conserved residues are shown on a yellow background. Residues from EMBP involved in interactions with sulfate ions are marked with red triangles. This picture was generated using the program ALSCRIPT (60).

Figure 2.
Fig. 2. A, stereoview comparing interactions between EMBP and sulfate ions S1 and S2 with those between EMBP and the modeled disaccharide component of heparan sulfate (top). Equivalent comparison involving S5 and S8 (bottom). Sulfate ions from the EMBP structure are shown in black (oxygen atoms) and orange (sulfur atom). The modeled carbohydrate is shown in green. Hydrogen bonds between sulfate ions and EMBP are shown as dashed lines; water molecules are colored cyan. B, nature and topology of the carbohydrate-binding sites of EMBP and MBP depicted as surface representations and colored by electrostatic potential. Representation of EMBP surface in complex with sulfate ions (left), with modeled disaccharide IdoA(2-OSO[3])-GlcNSO[3](6-OSO[3]), a repeating component of heparin and heparan sulfate (middle) and representation of rat mannose-binding protein in complex with -methyl-D-galactoside (PDB Code: 1AFA) (right). The color coding is 15 T/e (red) to +15 T/e (blue) for EMBP, 10 T/e (red) to +10 T/e (blue) for MBP, where is the Poisson-Boltzmann constant at temperature T (Kelvin) per electron e, as generated by the program GRASP (61).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 26197-26203) copyright 2001.

Figures were selected by the author.