Structural Basis for Signaling Through Shared Common γ Chain Cytokines

Adv Exp Med Biol. 2019:1172:1-19. doi: 10.1007/978-981-13-9367-9_1.

Abstract

The common γ chain (γc) family of hematopoietic cytokines consists of six distinct four α-helix bundle soluble ligands that signal through receptors which include the shared γc subunit to coordinate a wide range of physiological processes, in particular, those related to innate and adaptive immune function. Since the first crystallographic structure of a γc family cytokine/receptor signaling complex (the active Interleukin-2 [IL-2] quaternary complex) was determined in 2005 [1], tremendous progress has been made in the structural characterization of this protein family, transforming our understanding of the molecular mechanisms underlying immune activity. Although many conserved features of γc family cytokine complex architecture have emerged, distinguishing details have been observed for individual cytokine complexes that rationalize their unique functional properties. Much work remains to be done in the molecular characterization of γc family signaling, particularly with regard to intracellular activation events, and looking forward, new technologies in structural biophysics will offer further insight into the biology of cytokine signaling to inform the design of targeted therapeutics for treatment of immune-linked diseases such as cancer, infection, and autoimmune disorders.

Keywords: Common γ chain; Cytokine; Interleukin; Lymphocytes; Protein crystallography; Structural immunology.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Interleukin Receptor Common gamma Subunit* / chemistry
  • Interleukin Receptor Common gamma Subunit* / physiology
  • Interleukin-2 / chemistry
  • Interleukin-2 / physiology
  • Receptors, Cytokine / metabolism
  • Signal Transduction* / physiology

Substances

  • Interleukin Receptor Common gamma Subunit
  • Interleukin-2
  • Receptors, Cytokine