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Structure–Function Relationships of Antimicrobial Chemokines

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Antimicrobial Peptides and Innate Immunity

Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

The chemokines are a group of small chemotactic cytokines that play an important role in the innate and adaptive immune system. Their main function is related to the recruitment of white blood cells to sites of infection. They bind to specific chemokine receptors, which subsequently triggers signaling pathways in the leukocytes. Recently the discovery of chemokines that possess a direct antimicrobial activity against a broad range of pathogenic bacteria has generated increased interest in the role of these proteins in the innate immune system. Prior studies regarding ligand and receptor binding have already established the structural elements important for chemokine interaction and activation of their receptors. In the same manner, it is important to study the structural features required for the antimicrobial activity of this group of chemokines in order to establish key elements related with this new activity. This review will focus on the structure–function relationships that appear to be related to the direct antimicrobial activity of the chemokines. A close similarity of the C-terminal domain of many chemokines to cationic α-helical antimicrobial peptides suggests that this C-terminal helical region is responsible for the chemokine antimicrobial activity. However, for several chemokines, the antimicrobial activity resides in other parts of the protein, indicating that each chemokine needs to be examined individually. We also discuss the role of dimerization and of linearization of chemokines in their antimicrobial activity.

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Abbreviations

AMPs:

Antimicrobial peptides

CA-MRSA:

Community-associated methicillin-resistant Staphylococcus aureus

CTAP-3:

Connective tissue-activating protein-3

DC:

Dendritic cells

DOPE:

1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine

DOPG:

1,2-Dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol)

ENA-78:

Epithelial neutrophil-activating protein 78

GCP-2:

Granulocyte chemotactic protein-2

GRO:

Growth-regulated oncogene

hBD:

Human beta-defensin

IL-8:

Interleukin-8

IP-10:

Interferon-inducible protein-10

I-TAC:

Interferon-inducible T-cell alpha chemoattractant

LDL:

Low-density lipoprotein

MCP-4:

Monocyte chemoattractant protein-4

MEC:

Mucosa-associated epithelial chemokine

MIG:

Monokine induced IFN-gamma

MIP-3α:

Human macrophage inflammatory protein-3α

NAP-2:

Neutrophil-activating peptide-2

NMR:

Nuclear magnetic resonance

PBP:

Platelet basic protein

PF-4:

Platelet factor-4

PG-1:

Protegrin-1

PGLa:

Peptidyl-glycylleucine-carboxyamide

PMP:

Platelet microbicidal protein

RANTES:

Regulated upon activation normal T-cell expressed and secreted

SDS:

Sodium dodecyl sulfate

SIC:

Streptococcal inhibitor of complement

SPA:

Staphylococcal protein A

SpyCEP:

Streptococcus pyogenes cell envelope proteinase

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Acknowledgments

We are grateful to Dr. Leo Nguyen and Dr. David Chan for providing the PDB files for full-length NAP-2 and TC-1 and to Dr. P.H.S. Kwakman and Dr. J. Krijgsveld for sharing unpublished results on thrombocidin-1.

  This work has been funded by an operating grant from the “Novel Alternatives to Antibiotics” program of the Canadian Institutes of Health Research to Dr. Hans J. Vogel. Mauricio Arias and Dr. Hans J. Vogel are the holders of a Studentship and a Scientist award, respectively, of the Alberta Heritage Foundation for Medical Research.

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Authors and Affiliations

  1. Department of Biological Sciences, Biochemistry Research Group, University of Calgary, 2500 University Dr. NW, Calgary, AB, Canada

    Mauricio Arias & Hans J. Vogel

  2. Department of Medical Microbiology, Centre for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands

    Sebastian A. J. Zaat

Authors
  1. Mauricio Arias
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  2. Sebastian A. J. Zaat
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  3. Hans J. Vogel
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Correspondence to Hans J. Vogel .

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Editors and Affiliations

  1. , Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2300 RC, Netherlands

    Pieter S. Hiemstra

  2. Ctr for Infection & Immun. Amsterdam, Dept. Medical Microbiology, University of Amsterdam, Meibergdreef 15, Amsterdam, 1105 AZ, Netherlands

    Sebastian A. J. Zaat

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Arias, M., Zaat, S.A.J., Vogel, H.J. (2013). Structure–Function Relationships of Antimicrobial Chemokines. In: Hiemstra, P., Zaat, S. (eds) Antimicrobial Peptides and Innate Immunity. Progress in Inflammation Research. Springer, Basel. https://doi.org/10.1007/978-3-0348-0541-4_8

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  • DOI: https://doi.org/10.1007/978-3-0348-0541-4_8

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