PDBsum entry: 1nr4

Cytokine

PDB id: 1nr4

Contents

Protein chains

67 a.a. *

64 a.a. *

66 a.a. *

Ligands

SO4 ×6

Waters ×647

* Residue conservation analysis

PDB id:

1nr4

Name:

Cytokine

Title:

High resolution crystal structures of thymus and activation- regulated chemokine

Structure:

Thymus and activation-regulated chemokine. Chain: a, b, c, d, e, f, g, h. Synonym: small inducible cytokine a17. Ccl17. Cc chemokine tarc. T cell-directed cc. Engineered: yes

Source:

Synthetic: yes. Other_details: this sequence occurs naturally in humans

Biol. unit:

Dimer (from PQS)

Resolution:

1.72Å R-factor: 0.201 R-free: 0.239

Authors:

O.A.Asojo,C.Boulegue,D.M.Hoover,W.Lu,J.Lubkowski

Key ref:

O.A.Asojo et al. (2003). Structures of thymus and activation-regulated chemokine (TARC). Acta Crystallogr D Biol Crystallogr, 59, 1165-1173. PubMed id: 12832759 DOI: 10.1107/S0907444903009454

Date:

23-Jan-03 Release date: 05-Aug-03

Protein chains

Q92583  (CCL17_HUMAN) -  C-C motif chemokine 17

Seq: 94 a.a.

Struc: 67 a.a.

Protein chains

Q92583  (CCL17_HUMAN) -  C-C motif chemokine 17

Seq: 94 a.a.

Struc: 64 a.a.

Protein chains

Q92583  (CCL17_HUMAN) -  C-C motif chemokine 17

Seq: 94 a.a.

Struc: 66 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (2 terms)
• Biological process: immune response (6 terms)
• Biochemical function: receptor binding (3 terms)

DOI no: 10.1107/S0907444903009454

Acta Crystallogr D Biol Crystallogr 59:1165-1173 (2003)

PubMed id: 12832759

Structures of thymus and activation-regulated chemokine (TARC).

O.A.Asojo, C.Boulègue, D.M.Hoover, W.Lu, J.Lubkowski.

ABSTRACT

Thymus and activation-regulated chemokine (TARC) is a CC chemokine that is mainly expressed in the thymus. TARC interacts primarily with the CCR4 receptor and to a lesser extent with the CCR8 receptor. The structures of TARC have been solved by molecular replacement in two space groups, triclinic (P1) and tetragonal (P4(1)), and refined to resolutions of 1.72 and 2.1 A, respectively, with R factors of 19.8% (R(free) = 24.1%) and 19.8% (R(free) = 27.7%), respectively. The search model originated from the crystal structure of another chemokine, RANTES, and proved to be only modestly similar to the refined structure of TARC. Whereas the tetragonal structure was easily solved using the program AMoRe, solution of the triclinic structure proved to be quite challenging and was obtained by combining the results from four different molecular-replacement programs (AMoRe, CNS, BEAST and EPMR), with subsequent extension of the gathered information. The tertiary structure of TARC is similar to that of other CC chemokines, with a three-stranded antiparallel beta-sheet flanked by a C-terminal helix. Both quaternary structures consist of dimers, which in the triclinic crystals pack further into tetramers. The TARC dimers are similar to those observed previously in the crystal structures of both MCP-1 and RANTES.

Selected figure(s)

Figure 5.
Figure 5 Primary structures of SLC, TARC, RANTES, MIP-1 , MCP-1, MIP-1 , mutRANTES and FKN show well conserved sequences.

Figure 6.
Figure 6 (a) Overlay of the structures of TARC (aquamarine), MIP-1 (magenta), MCP-1 (red), FKN (blue), MIP-1 (blue-violet) and RANTES (yellow) show how well the CC chemokines align; the putative heparin-binding residues are shown in ball-and-stick representation. (b)-(g) Charge distribution on surfaces of the CC chemokines, (b) TARC, (c) RANTES, (d) MIP-1 , (e) MCP-1, (f) MIP-1 , (g) mutRANTES and (h) FKN, shown in the same orientation as Fig. 6-(a), correlates with the avidity of heparin binding. Note that regions around residues Lys47, Lys55 and Lys56 are more basic (blue) in TARC than in the others.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2003, 59, 1165-1173) copyright 2003.

Figures were selected by an automated process.