PDBsum entry: 1m8a

Cytokine

PDB id: 1m8a

Contents

Protein chains

61 a.a. *

Ligands

IPA ×10

Waters ×169

* Residue conservation analysis

PDB id:

1m8a

Name:

Cytokine

Title:

Human mip-3alpha/ccl20

Structure:

Small inducible cytokine a20. Chain: a, b. Synonym: cc-chemokine larc, mip-3-alpha, ccl20, macrophage inflammatory protein 3 alpha, liver and activation- regulated chemokine, beta chemokine exodus-1. Engineered: yes

Source:

Synthetic: yes. Other_details: the protein was synthesized using machine- assisted stepwise solid phase peptide synthesis on an applied biosystems 433a synthesizer using a custom- designed program tailored from the published in situ neutralization/hbtu activation protocol for boc chemistry (schnolzer, m. Et al. (1992) j.Pept.Protein res. 40, 180- 193). It is naturally found in homo sapiens (human).

Resolution:

1.70Å R-factor: 0.190 R-free: 0.238

Authors:

D.M.Hoover,C.Boulegue,D.Yang,J.J.Oppenheim,K.Tucker,W.Lu, J.Lubkowski

Key ref:

D.M.Hoover et al. (2002). The structure of human macrophage inflammatory protein-3alpha /CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins. J Biol Chem, 277, 37647-37654. PubMed id: 12149255 DOI: 10.1074/jbc.M203907200

Date:

24-Jul-02 Release date: 31-Jul-02

Protein chains

P78556  (CCL20_HUMAN) -  C-C motif chemokine 20

Seq: 96 a.a.

Struc: 61 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (2 terms)
• Biological process: immune response (7 terms)
• Biochemical function: cytokine activity (2 terms)

DOI no: 10.1074/jbc.M203907200

J Biol Chem 277:37647-37654 (2002)

PubMed id: 12149255

The structure of human macrophage inflammatory protein-3alpha /CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins.

D.M.Hoover, C.Boulegue, D.Yang, J.J.Oppenheim, K.Tucker, W.Lu, J.Lubkowski.

ABSTRACT

Human macrophage inflammatory protein-3alpha (MIP-3alpha; CCL20) is a CC-type chemokine that binds to and activates CC chemokine receptor-6 (CCR6). Although MIP-3alpha does not share the binding site of CCR6 with any other chemokine, human beta-defensin-1 and -2, small cationic antimicrobial peptides, have also been found to bind to and activate CCR6. Conversely, we have found that MIP-3alpha possesses antibacterial activity of greater potency than human beta-defensin-1 and -2 against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213, while having no activity against the fungus Candida albicans. There is no clear sequence similarity between beta-defensins and the chemokine MIP-3alpha, beyond an abundance of cationic residues and the presence of disulfide bonds. Nonetheless, there are structural similarities between these three proteins that allow their overlap of chemotactic and antimicrobial activities. In this report, we describe the x-ray crystal structure of human MIP-3alpha refined to a resolution of 1.7 A and compare it with the crystal structures of human beta-defensin-1 and -2. Molecules of MIP-3alpha and the beta-defensins seem to share few structural motifs that are likely associated with their common biological activities.

Selected figure(s)

Figure 2.
Fig. 2. Stereo drawing of the MIP-3 dimer. In each monomer, the peptide chain begins at Asp5 and ends at Lys65. This figure was generated using the program RIBBONS (74).

Figure 3.
Fig. 3. Close-up stereo view of Trp55 rotated into solvent. The interaction between crystallographically related monomers A (shown in blue) and B (shown in red) near Trp55 is shown. Two isopropyl alcohol molecules (ipOH) are also shown. Leu15 rotates slightly into the pocket vacated by Trp55. Simultaneously, the peptide between Leu15 and His16 rotates to form a hydrogen bond with the indole nitrogen of the Trp55 side chain. Van der Waals contacts are made between Trp55A and Tyr58A, Ile^59A, Ile^14B, Leu54B, Trp55B, Tyr58B, and an isopropyl alcohol molecule.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 37647-37654) copyright 2002.

Figures were selected by an automated process.