Chemokine oligomerization in cell signaling and migration - PubMed (original) (raw)

Review

Chemokine oligomerization in cell signaling and migration

Xu Wang et al. Prog Mol Biol Transl Sci. 2013.

Abstract

Chemokines are small proteins best known for their role in controlling the migration of diverse cells, particularly leukocytes. Upon binding to their G-protein-coupled receptors on the leukocytes, chemokines stimulate the signaling events that cause cytoskeletal rearrangements involved in cell movement, and migration of the cells along chemokine gradients. Depending on the cell type, chemokines also induce many other types of cellular responses including those related to defense mechanisms, cell proliferation, survival, and development. Historically, most research efforts have focused on the interaction of chemokines with their receptors, where monomeric forms of the ligands are the functionally relevant state. More recently, however, the importance of chemokine interactions with cell surface glycosaminoglycans has come to light, and in most cases appears to involve oligomeric chemokine structures. This review summarizes existing knowledge relating to the structure and function of chemokine oligomers, and emerging methodology for determining structures of complex chemokine assemblies in the future.

Copyright © 2013 Elsevier Inc. All rights reserved.

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Figures

Figure 20.1

Figure 20.1

Monomeric structure of the chemokine RANTES (CCL5) (PDB ID 1U4L).

Figure 20.2

Figure 20.2

Dimer structures of chemokines. Monomeric units in each dimer are colored light or dark gray. The PDB ID of each structure is shown in parentheses.

Figure 20.3

Figure 20.3

Known quaternary structures of chemokines. Each dimeric unit is colored in light and dark gray alternately. The PDB ID of each structure is shown in parentheses.

Figure 20.4

Figure 20.4

GAG-binding motifs of chemokines. Amino acids known to bind GAGs are shown as black sticks. The same residues are also colored black on the oligomer surface depiction. For IL-8 (CXCL8), K20, R60, K64, K67, and R68 are shown. For MCP-1 (CCL2), R18, K19, R24, K49, K58, and H66 are shown. For MIP1α (CCL3), R18, K45, R46, and K48 are shown. For RANTES (CCL5), R17, K44, R45, and K47 are shown.

Figure 20.5

Figure 20.5

Chemical shift perturbation on addition of a four-sufated chondroitin sulfate hexamer to 15N-labeled RANTES (CCL5). A series of 15N–1H HSQC spectra are superimposed to show chemical shift changes as increasing amounts of the hexamer are added. Among cross-peaks shifting are those assigned to residues from the BBXB motif, R44, K45, N46, R47. Spectra are taken at 600 MHz for 1H on a ~400 μM, pH 3.5, sample of wild-type RANTES (CCL5).

Figure 20.6

Figure 20.6

Native-spray analysis of 10 μM wild-type RANTES (CCL5) at pH 4.5. Only even numbered oligomers are observed from dimer to octamer, indicating that the RANTES (CCL5) oligomer is assembled via concatenation of the dimer subunit.

Figure 20.7

Figure 20.7

Hydroxyl radical protein footprinting of wild-type RANTES (CCL5) at pH 4.5 (tetramer) compared to the E66S mutant at pH 4.5 (dimer) mapped on a model of the RANTES (CCL5) tetramer. Regions of weak protection (<1.5× reduction in oxidation) from oxidation in the wild-type compared to the E66S mutant (gray) are found in the monomer–monomer interface and can be explained by decrease in free monomer in the wild-type sample. Regions of strong protection (>2× reduction in oxidation) from oxidation in the wild-type compared to the E66S mutant (black) are not in the monomer–monomer interface, and are therefore protected by the dimer–dimer interaction.

Figure 20.8

Figure 20.8

Hydroxyl radical protein footprinting of wild-type RANTES (CCL5) at pH 4.5 (tetramer) compared to pH 7 (large oligomers) mapped on a model of the RANTES (CCL5) octamer. Regions of complete protection from oxidation at pH 7 but found heavily oxidized at pH 4.5 (black) are found at the dimer–dimer interface, while regions of partial protection at pH 7 compared to pH 4.5 (gray) are found at the monomer–monomer interface. These pattern of protection mirrors the results found for the comparison of wild-type RANTES (CCL5) at pH 4.5 (tetramer) compared to the E66S mutant at pH 4.5 (dimer), with the extent of protection increasing dramatically.

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References

    1. Goodsell DS, Olson AJ. Structural symmetry and protein function. Annu Rev Biophys Biomol Struct. 2000;29:105–53. - PubMed
    1. Levy ED, Pereira-Leal JB, Chothia C, Teichmann SA. 3D complex: a structural classification of protein complexes. PLoS Comput Biol. 2006;2(11):1395–406. - PMC - PubMed
    1. Ali MH, Imperiali B. Protein oligomerization: how and why. Bioorg Med Chem. 2005;13 (17):5013–20. - PubMed
    1. Sallusto F, Baggiolini M. Chemokines and leukocyte traffic. Nat Immunol. 2008;9 (9):949–52. - PubMed
    1. Baggiolini M. Chemokines and leukocyte traffic. Nature. 1998;392(6676):565–8. - PubMed

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