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Evolutionary Features in the Structure and Function of Bacterial Toxins

Toxins can function both as a harmful and therapeutic molecule, depending on their concentrations. The diversity in their function allows us to ask some very pertinent questions related to their origin and roles: (a) What makes them such effective molecules? (b) Are there evolutionary features encod...

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Autores principales: Kumar, Raj, Feltrup, Thomas M., Kukreja, Roshan V., Patel, Kruti B., Cai, Shuowei, Singh, Bal Ram
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356308/
https://www.ncbi.nlm.nih.gov/pubmed/30609803
http://dx.doi.org/10.3390/toxins11010015
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author Kumar, Raj
Feltrup, Thomas M.
Kukreja, Roshan V.
Patel, Kruti B.
Cai, Shuowei
Singh, Bal Ram
author_facet Kumar, Raj
Feltrup, Thomas M.
Kukreja, Roshan V.
Patel, Kruti B.
Cai, Shuowei
Singh, Bal Ram
author_sort Kumar, Raj
collection PubMed
description Toxins can function both as a harmful and therapeutic molecule, depending on their concentrations. The diversity in their function allows us to ask some very pertinent questions related to their origin and roles: (a) What makes them such effective molecules? (b) Are there evolutionary features encoded within the structures of the toxins for their function? (c) Is structural hierarchy in the toxins important for maintaining their structure and function? (d) Do protein dynamics play a role in the function of toxins? and (e) Do the evolutionary connections to these unique features and functions provide the fundamental points in driving evolution? In light of the growing evidence in structural biology, it would be appropriate to suggest that protein dynamics and flexibility play a much bigger role in the function of the toxin than the structure itself. Discovery of IDPs (intrinsically disorder proteins), multifunctionality, and the concept of native aggregation are shaking the paradigm of the requirement of a fixed three-dimensional structure for the protein’s function. Growing evidence supporting the above concepts allow us to redesign the structure-function aspects of the protein molecules. An evolutionary model is necessary and needs to be developed to study these important aspects. The criteria for a well-defined model would be: (a) diversity in structure and function, (b) unique functionality, and (c) must belong to a family to define the evolutionary relationships. All these characteristics are largely fulfilled by bacterial toxins. Bacterial toxins are diverse and widely distributed in all three forms of life (Bacteria, Archaea and Eukaryotes). Some of the unique characteristics include structural folding, sequence and functional combination of domains, targeting a cellular process to execute their function, and most importantly their flexibility and dynamics. In this work, we summarize certain unique aspects of bacterial toxins, including role of structure in defining toxin function, uniqueness in their enzymatic function, and interaction with their substrates and other proteins. Finally, we have discussed the evolutionary aspects of toxins in detail, which will help us rethink the current evolutionary theories. A careful study, and appropriate interpretations, will provide answers to several questions related to the structure-function relationship of proteins, in general. Additionally, this will also allow us to refine the current evolution theories.
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spelling pubmed-63563082019-02-05 Evolutionary Features in the Structure and Function of Bacterial Toxins Kumar, Raj Feltrup, Thomas M. Kukreja, Roshan V. Patel, Kruti B. Cai, Shuowei Singh, Bal Ram Toxins (Basel) Review Toxins can function both as a harmful and therapeutic molecule, depending on their concentrations. The diversity in their function allows us to ask some very pertinent questions related to their origin and roles: (a) What makes them such effective molecules? (b) Are there evolutionary features encoded within the structures of the toxins for their function? (c) Is structural hierarchy in the toxins important for maintaining their structure and function? (d) Do protein dynamics play a role in the function of toxins? and (e) Do the evolutionary connections to these unique features and functions provide the fundamental points in driving evolution? In light of the growing evidence in structural biology, it would be appropriate to suggest that protein dynamics and flexibility play a much bigger role in the function of the toxin than the structure itself. Discovery of IDPs (intrinsically disorder proteins), multifunctionality, and the concept of native aggregation are shaking the paradigm of the requirement of a fixed three-dimensional structure for the protein’s function. Growing evidence supporting the above concepts allow us to redesign the structure-function aspects of the protein molecules. An evolutionary model is necessary and needs to be developed to study these important aspects. The criteria for a well-defined model would be: (a) diversity in structure and function, (b) unique functionality, and (c) must belong to a family to define the evolutionary relationships. All these characteristics are largely fulfilled by bacterial toxins. Bacterial toxins are diverse and widely distributed in all three forms of life (Bacteria, Archaea and Eukaryotes). Some of the unique characteristics include structural folding, sequence and functional combination of domains, targeting a cellular process to execute their function, and most importantly their flexibility and dynamics. In this work, we summarize certain unique aspects of bacterial toxins, including role of structure in defining toxin function, uniqueness in their enzymatic function, and interaction with their substrates and other proteins. Finally, we have discussed the evolutionary aspects of toxins in detail, which will help us rethink the current evolutionary theories. A careful study, and appropriate interpretations, will provide answers to several questions related to the structure-function relationship of proteins, in general. Additionally, this will also allow us to refine the current evolution theories. MDPI 2019-01-03 /pmc/articles/PMC6356308/ /pubmed/30609803 http://dx.doi.org/10.3390/toxins11010015 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kumar, Raj
Feltrup, Thomas M.
Kukreja, Roshan V.
Patel, Kruti B.
Cai, Shuowei
Singh, Bal Ram
Evolutionary Features in the Structure and Function of Bacterial Toxins
title Evolutionary Features in the Structure and Function of Bacterial Toxins
title_full Evolutionary Features in the Structure and Function of Bacterial Toxins
title_fullStr Evolutionary Features in the Structure and Function of Bacterial Toxins
title_full_unstemmed Evolutionary Features in the Structure and Function of Bacterial Toxins
title_short Evolutionary Features in the Structure and Function of Bacterial Toxins
title_sort evolutionary features in the structure and function of bacterial toxins
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356308/
https://www.ncbi.nlm.nih.gov/pubmed/30609803
http://dx.doi.org/10.3390/toxins11010015
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