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Assessment of Lymphocyte Migration in an Ex Vivo Transmigration System
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Published on: September 20, 2019

Structural perspectives on antimicrobial chemokines.

Leonard T Nguyen1, Hans J Vogel

  • 1Biochemistry Research Group, Department of Biological Sciences, University of Calgary Calgary, AB, Canada.

Frontiers in Immunology
|January 8, 2013
PubMed
Summary
This summary is machine-generated.

Chemokines, known for immune signaling, also possess direct antimicrobial activity due to their positive charge. Structural studies using NMR reveal how these proteins and their fragments exert microbicidal actions.

Keywords:
antimicrobial peptidechemokinechemokine oligomerizationchemokine structureglycosaminoglycan

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Immunology

Background:

  • Chemokines are primarily known as immune signaling proteins.
  • Emerging research reveals a significant antimicrobial role for human chemokines.
  • This dual function, or 'moonlighting', is linked to their high net positive charge.

Purpose of the Study:

  • To explore the structural basis of the direct antimicrobial activity of chemokines.
  • To investigate how structural features and dynamics contribute to the microbicidal actions of chemokines.
  • To elucidate the role of structural elements, oligomerization, and interactions in chemokine antimicrobial function.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy for structure and dynamics determination.
  • NMR relaxation experiments to study protein dynamics.
  • NMR diffusion experiments to analyze monomer-dimer equilibria.
  • NMR chemical shift perturbation to map subunit interfaces.
  • Structural determination of chemokines in complex with glycosaminoglycans.

Main Results:

  • Antimicrobial activity is associated with specific structural elements, particularly α-helical regions.
  • NMR studies provide insights into the solution structures and dynamics of intact chemokines and their variants.
  • Oligomerization states and interactions with glycosaminoglycans influence antimicrobial function.
  • The structural plasticity of chemokines, like XCL1/lymphotactin, is characterized.

Conclusions:

  • Structural insights derived from NMR spectroscopy are crucial for understanding chemokine antimicrobial mechanisms.
  • The positive charge, amphipathic structures, and dynamic behavior of chemokines underpin their direct microbicidal effects.
  • Further structural characterization is key to fully understanding the multifaceted roles of chemokines.