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Published on: April 12, 2019
Circular proteins and mechanisms of cyclization
Brendon F Conlan1, Amanda D Gillon, David J Craik
1Department of Biochemistry, La Trobe University, Melbourne, Victoria 3086, Australia.
Biopolymers
|June 22, 2010
Summary
Cyclic proteins, though rare, exhibit remarkable stability due to head-to-tail linkages. This review summarizes known mechanisms of protein cyclization and their occurrence across species.
Area of Science:
- Biochemistry
- Molecular Biology
- Proteomics
Background:
- Protein cyclization, a rare post-translational modification, results in exceptionally stable cyclic proteins.
- The precise mechanisms driving protein cyclization remain incompletely understood.
- Cyclic proteins are conserved across prokaryotic and eukaryotic organisms, including bacteriocins, pilins, theta defensins, retrocyclins, sunflower trypsin inhibitor, and cyclotides.
Purpose of the Study:
- To review and summarize the known mechanisms and events leading to protein cyclization.
- To highlight the prevalence and diversity of cyclic proteins in nature.
- To elucidate the role of specific enzymes, such as cysteine proteases, in mediating cyclization.
Main Methods:
- Literature review of studies on protein cyclization mechanisms.
- Analysis of known examples of cyclic proteins from prokaryotic and eukaryotic species.
- Examination of the enzymatic processing of cyclotides by asparaginyl endopeptidase.
Main Results:
- Cyclization confers exceptional stability to proteins.
- Cyclic proteins are found in diverse species, including bacteria, mammals, and plants.
- Specific cysteine proteases, like the asparaginyl endopeptidase in Oldenlandia affinis, play a key role in cyclotide processing via transpeptidation.
Conclusions:
- Protein cyclization is a significant but understudied modification enhancing protein stability.
- Enzymatic processing, particularly by cysteine proteases, is crucial for generating cyclic peptides.
- Understanding these mechanisms can inform the design of stable peptide-based therapeutics.
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