Divide, conquer and reconstruct: How to solve the 3D structure of recalcitrant Micro-Exon Gene (MEG) protein from Schistosoma mansoni

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00575284" target="_blank" >RIV/61388963:_____/23:00575284 - isvavai.cz</a>
Alternative codes found
RIV/60460709:41210/23:N0000007 RIV/60460709:41330/23:97523
Result on the web
<a href="https://doi.org/10.1371/journal.pone.0289444" target="_blank" >https://doi.org/10.1371/journal.pone.0289444</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1371/journal.pone.0289444" target="_blank" >10.1371/journal.pone.0289444</a>

Result language
angličtina
Original language name
Divide, conquer and reconstruct: How to solve the 3D structure of recalcitrant Micro-Exon Gene (MEG) protein from Schistosoma mansoni
Original language description
Micro-Exon Genes are a widespread class of genes known for their high variability, widespread in the genome of parasitic trematodes such as Schistosoma mansoni. In this study, we present a strategy that allowed us to solve the structures of three alternatively spliced isoforms from the Schistoma mansoni MEG 2.1 family for the first time. All isoforms are hydrophobic, intrinsically disordered, and recalcitrant to be expressed in high yield in heterologous hosts. We resorted to the chemical synthesis of shorter pieces, before reconstructing the entire sequence. Here, we show that isoform 1 partially folds in a-helix in the presence of trifluoroethanol while isoform 2 features two rigid elbows, that maintain the peptide as disordered, preventing any structuring. Finally, isoform 3 is dominated by the signal peptide, which folds into a-helix. We demonstrated that combining biophysical techniques, like circular dichroism and nuclear magnetic resonance at natural abundance, with in silico molecular dynamics simulation for isoform 1 only, was the key to solve the structure of MEG 2.1. Our results provide a crucial piece to the puzzle of this elusive and highly variable class of proteins.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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