PDBsum entry: 1eot

Cytokine

PDB id: 1eot

Contents

Protein chain

74 a.a. *

* Residue conservation analysis

PDB id:

1eot

Name:

Cytokine

Title:

Solution nmr structure of eotaxin, minimized average structure

Structure:

Eotaxin. Chain: a. Engineered: yes. Other_details: both synthetic and recombinant samples were prepared. Recombinant samples were uniformly labelled with n15.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Other_details: both synthetic and recombinant samples were prepared yes

NMR struc:

1 models

Authors:

M.P.Crump,K.Rajarathnam,B.D.Sykes

Key ref:

M.P.Crump et al. (1998). Solution structure of eotaxin, a chemokine that selectively recruits eosinophils in allergic inflammation. J Biol Chem, 273, 22471-22479. PubMed id: 9712872 DOI: 10.1074/jbc.273.35.22471

Date:

17-Jun-98 Release date: 13-Jan-99

Protein chain

P51671  (CCL11_HUMAN) -  Eotaxin

Seq: 97 a.a.

Struc: 74 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (2 terms)
• Biological process: mammary duct terminal end bud growth (22 terms)
• Biochemical function: cytokine activity (2 terms)

DOI no: 10.1074/jbc.273.35.22471

J Biol Chem 273:22471-22479 (1998)

PubMed id: 9712872

Solution structure of eotaxin, a chemokine that selectively recruits eosinophils in allergic inflammation.

M.P.Crump, K.Rajarathnam, K.S.Kim, I.Clark-Lewis, B.D.Sykes.

ABSTRACT

The solution structure of the CCR3-specific chemokine, eotaxin, has been determined by NMR spectroscopy. The quaternary structure of eotaxin was investigated by ultracentrifugation and NMR, and it was found to be in equilibrium between monomer and dimer under a wide range of conditions. At pH </= 5 and low ionic strength, eotaxin was found to be predominantly a monomer. The three-dimensional structure of the eotaxin monomer solved at pH 5.0 revealed that it has a typical chemokine fold, which includes a 3-stranded beta-sheet and an overlying alpha-helix. Except for the N-terminal residues (residues 1-8), the core of the protein is well defined. The eotaxin structure is compared with the chemokines regulated upon activation, normal T-cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 (MCP-1); eotaxin binds only CC chemokine receptor CCR3, whereas RANTES binds many receptors including CCR3, and MCP-1 binds a distinct receptor, CCR2. The RMSD of the eotaxin ensemble of structures with the RANTES average minimized monomeric subunit is 5.52 +/- 0.87 A over all backbone atoms and 1.14 +/- 0.09 A over backbone atoms of residues 11-28 and 34-65. The most important difference between the structures is in the N-terminal residues that are unstructured in eotaxin but structured in RANTES and MCP-1. Several residues in the loop region of RANTES show similar packing in eotaxin (residues 11-17). As the N-terminal and loop regions have been shown to be critical for receptor binding and signaling, this structure will be useful for determining the basis for CCR3 selectivity of the eotaxin.

Selected figure(s)

Figure 4.
Fig. 4. Ensemble and average minimized structure of eotaxin. A, superimposition of the 32 simulated annealing structures of eotaxin on the average structure. The average structure was generated by averaging the coordinates of the 32 final eotaxin structures. The structures were overlaid on the average structure using just the backbone N, C , and C atoms of residues 9-68. B, in an orientation that optimizes clarity, the heavy atoms of well ordered side chains are labeled and superimposed on the average structure. The N and C termini are omitted for clarity. C, in the same orientation, a schematic diagram showing the restrained minimized average structure of eotaxin created with the program MOLSCRIPT (38). In this representation the helix is represented as a flat ribbon and the sheet with a broad arrow. The loops and turns are represented by a slim ribbon.

Figure 5.
Fig. 5. A, comparison of the tertiary structures of eotaxin, RANTES, and MCP-1. The minimized mean structure of one monomeric unit of both RANTES (blue, protein data base accession code 1RTO) and MCP-1 (yellow, protein data base accession code 1DOM) was used for overlaying on eotaxin (red). Backbone heavy atoms of the eotaxin minimized average structure excluding the N terminus and disulfides (residues 1-10) and the 30-s turn (residues 31-34) superimposed on MCP-1 (residues 13-32 and 37-69) with an RMSD of 1.29 Å. RANTES contains one less residue between the first -strand and the 30-s turn so eotaxin (residues 11-28 and 34-65) was superimposed on the minimized average monomeric subunit of RANTES (residues 12-29 and 34-65) giving an RMSD of 1.19 Å. B, comparison of ensembles of structures between RANTES dimer and eotaxin monomer.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1998, 273, 22471-22479) copyright 1998.

Figures were selected by an automated process.