The Diverse Functional Roles of Elongation Factor Tu (EF-Tu) in Microbial Pathogenesis.

Kate L Harvey,Steven P Djordjevic,Veronica M Jarocki,Ian G Charles

doi:10.3389/fmicb.2019.02351

Kate L Harvey, Steven P Djordjevic + Show 2 more

Open Access

https://doi.org/10.3389/fmicb.2019.02351

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Abstract

Elongation factor thermal unstable Tu (EF-Tu) is a G protein that catalyzes the binding of aminoacyl-tRNA to the A-site of the ribosome inside living cells. Structural and biochemical studies have described the complex interactions needed to effect canonical function. However, EF-Tu has evolved the capacity to execute diverse functions on the extracellular surface of both eukaryote and prokaryote cells. EF-Tu can traffic to, and is retained on, cell surfaces where can interact with membrane receptors and with extracellular matrix on the surface of plant and animal cells. Our structural studies indicate that short linear motifs (SLiMs) in surface exposed, non-conserved regions of the molecule may play a key role in the moonlighting functions ascribed to this ancient, highly abundant protein. Here we explore the diverse moonlighting functions relating to pathogenesis of EF-Tu in bacteria and examine putative SLiMs on surface-exposed regions of the molecule.

Highlights

Elongation Factor Thermo Unstable (EF-Tu) is one the most abundant proteins found in bacteria, comprising up to 6% of the total protein expressed in Escherichia coli (Furano, 1975) and as high as 10% of the total protein expressed in the genome reduced pathogen Mycoplasma pneumoniae (Dallo et al, 2002)
It is notable that cleavage fragments of Elongation factor thermal unstable Tu (EF-Tu) have been previously described in the cytoplasm and membrane fraction of L. monocytogenes (Archambaud et al, 2005) and more recently on the extracellular surfaces of S. aureus, Mycoplasma hyopneumoniae and M. pneumoniae (Widjaja et al, 2015, 2017)
EF-Tu has evolved to be a multifunctional protein in a wide variety of pathogenic bacteria

Summary

Introduction

Elongation Factor Thermo Unstable (EF-Tu) is one the most abundant proteins found in bacteria, comprising up to 6% of the total protein expressed in Escherichia coli (Furano, 1975) and as high as 10% of the total protein expressed in the genome reduced pathogen Mycoplasma pneumoniae (Dallo et al, 2002). This poses a challenge as signal secretion motifs are absent in this highly structured protein, and motifs required for binding diverse host cell surface receptor and matrix molecules must evolve without jeopardizing structural constraints needed to execute canonical function as a G protein. It is known that moonlighting proteins are processed on the surface of bacterial pathogens.

Results

Conclusion