The protein 14-3-3: A functionally versatile molecule in Giardia duodenalis

Adv Parasitol. 2019:106:51-103. doi: 10.1016/bs.apar.2019.08.002. Epub 2019 Sep 3.

Abstract

Giardia duodenalis is a cosmopolitan zoonotic protozoan parasite causing giardiasis, one of the most common diarrhoeal diseases in human and animals. Beyond its public health relevance, Giardia represents a valuable and fascinating model microorganism. The deep-branching phylogenetic position of Giardia, its simple life cycle and its minimalistic genomic and cellular organization provide a unique opportunity to define basal and "ancestral" eukaryotic functions. The eukaryotic 14-3-3 protein family represents a distinct example of phosphoserine/phosphothreonine-binding proteins. The extended network of protein-protein interactions established by 14-3-3 proteins place them at the crossroad of multiple signalling pathways that regulate physiological and pathological cellular processes. Despite the remarkable insight on 14-3-3 protein in different organisms, from yeast to humans, so far little attention was given to the study of this protein in protozoan parasites. However, in the last years, research efforts have provided evidences on unique properties of the single 14-3-3 protein of Giardia and on its association in key aspects of Giardia life cycle. In the first part of this chapter, a general overview of the features commonly shared among 14-3-3 proteins in different organisms (i.e. structure, target recognition, mode of action and regulatory mechanisms) is included. The second part focus on the current knowledge on the biochemistry and biology of the Giardia 14-3-3 protein and on the possibility to use this protein as target to propose new strategies for developing innovative antigiardial therapy.

Keywords: 14-3-3 protein; Encystation; Giardia duodenalis; Phosphorylation; Polyglycylation; Protein-protein interaction; Signal transduction; Small molecules PPI modulators.

Publication types

  • Review

MeSH terms

  • 14-3-3 Proteins / chemistry
  • 14-3-3 Proteins / genetics
  • 14-3-3 Proteins / metabolism*
  • Giardia / genetics
  • Giardia / metabolism*
  • Giardiasis / parasitology*
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*

Substances

  • 14-3-3 Proteins
  • Protozoan Proteins