In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 8 ( 2023-8-3), p. e0289444-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0289444
DOI:
10.1371/journal.pone.0289444.g001
DOI:
10.1371/journal.pone.0289444.g002
DOI:
10.1371/journal.pone.0289444.g003
DOI:
10.1371/journal.pone.0289444.g004
DOI:
10.1371/journal.pone.0289444.g005
DOI:
10.1371/journal.pone.0289444.g006
DOI:
10.1371/journal.pone.0289444.g007
DOI:
10.1371/journal.pone.0289444.t001
DOI:
10.1371/journal.pone.0289444.t002
DOI:
10.1371/journal.pone.0289444.s001
DOI:
10.1371/journal.pone.0289444.s002
DOI:
10.1371/journal.pone.0289444.r001
DOI:
10.1371/journal.pone.0289444.r002
DOI:
10.1371/journal.pone.0289444.r003
DOI:
10.1371/journal.pone.0289444.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2267670-3
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