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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-01-01
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| Series: | Toxins |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6651/11/1/15 |
| _version_ | 1828352197123899392 |
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| author | Raj Kumar Thomas M. Feltrup Roshan V. Kukreja Kruti B. Patel Shuowei Cai Bal Ram Singh |
| author_facet | Raj Kumar Thomas M. Feltrup Roshan V. Kukreja Kruti B. Patel Shuowei Cai Bal Ram Singh |
| author_sort | Raj Kumar |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-14T01:50:37Z |
| format | Article |
| id | doaj.art-44ab8a64d80348caaedfec3c41d93e1b |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-14T01:50:37Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-44ab8a64d80348caaedfec3c41d93e1b2022-12-22T02:19:22ZengMDPI AGToxins2072-66512019-01-011111510.3390/toxins11010015toxins11010015Evolutionary Features in the Structure and Function of Bacterial ToxinsRaj Kumar0Thomas M. Feltrup1Roshan V. Kukreja2Kruti B. Patel3Shuowei Cai4Bal Ram Singh5Botulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA 02747, USABotulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA 02747, USABotulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA 02747, USABotulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA 02747, USADepartment of Chemistry and Biochemistry, University of Massachusetts, Dartmouth, MA 02747, USABotulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA 02747, USAToxins 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.http://www.mdpi.com/2072-6651/11/1/15botulinum toxinevolutionsnare proteinsADP-ribosylationbacterial toxinanthrax toxincholera toxingluzincin clan |
| spellingShingle | Raj Kumar Thomas M. Feltrup Roshan V. Kukreja Kruti B. Patel Shuowei Cai Bal Ram Singh Evolutionary Features in the Structure and Function of Bacterial Toxins Toxins botulinum toxin evolution snare proteins ADP-ribosylation bacterial toxin anthrax toxin cholera toxin gluzincin clan |
| 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 | botulinum toxin evolution snare proteins ADP-ribosylation bacterial toxin anthrax toxin cholera toxin gluzincin clan |
| url | http://www.mdpi.com/2072-6651/11/1/15 |
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