Abstract
The cyclic miniprotein Momordica cochinchinensis Trypsin Inhibitor II (MCoTI-II) (34 amino acids) is a potent trypsin inhibitor (TI) and a favored scaffold for drug design. We have cloned the corresponding genes and determined that each precursor protein contains a tandem series of cyclic TIs terminating with the more commonly known, and potentially ancestral, acyclic TI. Expression of the precursor protein in Arabidopsis thaliana showed that production of the cyclic TIs, but not the terminal acyclic TI, depends on asparaginyl endopeptidase (AEP) for maturation. The nature of their repetitive sequences and the almost identical structures of emerging TIs suggest these cyclic peptides evolved by internal gene amplification associated with recruitment of AEP for processing between domain repeats. This is the third example of similar AEP-mediated processing of a class of cyclic peptides from unrelated precursor proteins in phylogenetically distant plant families. This suggests that production of cyclic peptides in angiosperms has evolved in parallel using AEP as a constraining evolutionary channel. We believe this is evolutionary evidence that, in addition to its known roles in proteolysis, AEP is especially suited to performing protein cyclization.
Abstract from the paper’s OpenAlex record, shown for indexing and research. Copyright remains with the authors or the publisher. Read at the source ↗
The text the model read, with the source record’s inline markup (italics, sub- and superscripts) rendered and its character entities decoded; quote offsets refer to the raw text.
Claims 7
Claim · model-written summary
Each cloned precursor contained tandem cyclic trypsin inhibitors ending in an acyclic inhibitor.
- Taxon
- Momordica cochinchinensis
Momordica cochinchinensise1 - Gene
- precursor proteine0
- Outcome
- tandem series of cyclic TIs terminating with the more commonly known, and potentially ancestral, acyclic TIe0
- Qualifier
- potentially ancestrale0
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
Verbatim
e0“We have cloned the corresponding genes and determined that each precursor protein contains a tandem series of cyclic TIs terminating with the more commonly known, and potentially ancestral, acyclic TI.”
e1“Momordica cochinchinensis Trypsin Inhibitor II”
Claim · model-written summary
Production of cyclic inhibitors in Arabidopsis depended on AEP.
- Taxon
- Arabidopsis thaliana
Arabidopsis thalianae0 - Gene
- asparaginyl endopeptidase (AEP)e0
- Outcome
- production of the cyclic TIse0
- Qualifier
- depends on asparaginyl endopeptidase (AEP) for maturatione0
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
Verbatim
e0“Expression of the precursor protein in Arabidopsis thaliana showed that production of the cyclic TIs, but not the terminal acyclic TI, depends on asparaginyl endopeptidase (AEP) for maturation.”
Claim · model-written summary
Production of terminal acyclic inhibitor in Arabidopsis did not depend on AEP.
- Taxon
- Arabidopsis thalianaArabidopsis thalianae0
- Gene
- asparaginyl endopeptidase (AEP)e0
- Outcome
- terminal acyclic TIe0
- Qualifier
- but not the terminal acyclic TIe0
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
Verbatim
e0“Expression of the precursor protein in Arabidopsis thaliana showed that production of the cyclic TIs, but not the terminal acyclic TI, depends on asparaginyl endopeptidase (AEP) for maturation.”
Claim · model-written summary
Repetitive sequence and structural similarity suggest internal gene amplification and AEP recruitment in cyclic peptide evolution.
- Taxon
- Momordica cochinchinensisMomordica cochinchinensise1
- Gene
- AEPe0
- Outcome
- cyclic peptides evolved by internal gene amplificatione0
- Qualifier
- processing between domain repeatse0
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
Verbatim
e0“The nature of their repetitive sequences and the almost identical structures of emerging TIs suggest these cyclic peptides evolved by internal gene amplification associated with recruitment of AEP for processing between domain repeats.”
e1“Momordica cochinchinensis Trypsin Inhibitor II”
Claim · model-written summary
Similar AEP processing of unrelated precursor proteins was found in distant plant families for a third time.
Verbatim
e0“This is the third example of similar AEP-mediated processing of a class of cyclic peptides from unrelated precursor proteins in phylogenetically distant plant families.”
Claim · model-written summary
Cyclic peptide production in angiosperms appears to have evolved in parallel through AEP.
- Taxon
- angiospermsMagnoliopsidae0
- Gene
- AEPe0
- Outcome
- production of cyclic peptidese0
- Qualifier
- evolved in parallele0
Verbatim
e0“This suggests that production of cyclic peptides in angiosperms has evolved in parallel using AEP as a constraining evolutionary channel.”
Claim · model-written summary
Authors infer that AEP is especially suited to protein cyclization.
- Taxon
- angiospermsMagnoliopsidae1
- Gene
- AEPe0
- Outcome
- protein cyclizatione0
- Qualifier
- especially suited to performing protein cyclizatione0
Verbatim
e0“We believe this is evolutionary evidence that, in addition to its known roles in proteolysis, AEP is especially suited to performing protein cyclization.”
e1“production of cyclic peptides in angiosperms”