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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.01670

Structural basis of the sub-cellular topology landscape of Escherichia coli

 Maria Loos1,  Reshmi Ramakrishnan1,  Wim Vranken2, Alexandra Tsirigotaki1, Evrydiki-Pandora Tsare3, Valentina Zorzini1, Jozefien De Geyter1, Biao Yuan1,  Ioannis Tsamardinos4,  Maria I. Klapa3, Joost Schymkowitz5, Frederic Rousseau5, Spyridoula Karamanou1 and  Tassos Economou1*
  • 1KU Leuven, Belgium
  • 2Free University of Brussels, Belgium
  • 3Foundation for Research and Technology Hellas, Greece
  • 4University of Crete, Greece
  • 5VIB & KU Leuven Center for Brain & Disease Research, Belgium

Cellular proteomes are distributed in multiple compartments: on DNA, ribosomes, on and inside membranes, or they become secreted. Structural properties that allow polypeptides to occupy subcellular niches, particularly to after crossing membranes, remain unclear. We compared intrinsic and extrinsic features in cytoplasmic and secreted polypeptides of the Escherichia coli K-12 proteome. Structural features between the cytoplasmome and secretome are sharply distinct, such that a signal peptide-agnostic machine learning tool distinguishes cytoplasmic from secreted proteins with 95.5% success. Cytoplasmic polypeptides are enriched in aliphatic, aromatic, charged and hydrophobic residues, unique folds and higher early folding propensities. Secretory polypeptides are enriched in polar/small amino acids, β folds, have higher backbone dynamics, higher disorder and contact order and are more often intrinsically disordered. These non-random distributions and experimental evidence imply that evolutionary pressure selected enhanced secretome flexibility, slow folding and looser structures, placing the secretome in a distinct protein class. These adaptations protect the secretome from premature folding during its cytoplasmic transit, optimize its lipid bilayer crossing and allowed it to acquire cell envelope specific chemistries. The latter may favour promiscuous multi-ligand binding, sensing of stress and cell envelope structure changes. In conclusion, enhanced flexibility, slow folding, looser structures and unique folds differentiate the secretome from the cytoplasmome. These findings have wide implications on the structural diversity and evolution of modern proteomes and the protein folding problem.

Keywords: protein domain, Protein Fold Class Prediction, Protein targeting and folding, protein targeting and transport, sub cellular topology, Protein Disorder, Protein disorder prediction, Protein disorder analysis, Chaperone, Protein fold classification, Sec (scretion) genes

Received: 12 Apr 2019; Accepted: 08 Jul 2019.

Edited by:

Baolei Jia, Chung-Ang University, South Korea

Reviewed by:

Vladimir N. Uversky, University of South Florida, United States
Oxana Galzitskaya, Institute of Protein Research (RAS), Russia  

Copyright: © 2019 Loos, Ramakrishnan, Vranken, Tsirigotaki, Tsare, Zorzini, De Geyter, Yuan, Tsamardinos, Klapa, Schymkowitz, Rousseau, Karamanou and Economou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Tassos Economou, KU Leuven, Leuven, Belgium, tassos.economou@kuleuven.be