Total synthesis and structural characterization of a novel protein scaffold from the snail Biomphalaria glabrata
Abstract
Disulfide-rich miniproteins constitute compact and highly stable scaffolds of growing interest for molecular and structural engineering. Schistosomins are $80-residue proteins conserved across gastropods that form a longstanding orphan family whose structure and biological roles have remained unknown. Here, we report the total chemical synthesis and structural characterization of a schistosomin isoform from Biomphalaria glabrata, a medically relevant intermediate host of the parasite Schistosoma mansoni. Using state-of-the-art solid-phase peptide synthesis, chemoselective peptide ligation, and controlled oxidative folding, we obtained homogeneous, wellfolded schistosomin suitable for biophysical and structural studies. High-resolution X-ray crystallography reveals a previously undescribed disulfide-rich fold defining a new class of miniprotein scaffold. Nano differential scanning fluorimetry and circular dichroism experiments demonstrate the remarkable thermal stability of this scaffold. Complementary in silico analyses suggest that the two naturally occurring isoforms, which differ by a single residue, exhibit highly similar structural and dynamic properties. Finally, transcript and protein analyses across snail tissues provide the first spatial expression map of schistosomin in a medically relevant mollusk. Together, this work establishes schistosomin as a novel and robust miniprotein scaffold and provides a structural and biological framework for exploring its function and potential applications.
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BibTeX
@article{melnyk2026total,
title = {{Total synthesis and structural characterization of a novel protein scaffold from the snail Biomphalaria glabrata}},
author = {Oleg Melnyk and Stéphanie Caby and Armelle Vigouroux and Christine Demanche and Rémi Desmet and Magalie Sénéchal and Benoît Snella and Alexandra Mougel and Céline Boidin‐wichlacz and Aurélie Parmentier and Ugo Pasco and Sonia Cantel and Solange Moréra and Jérôme Vicogne},
journal = {Protein Science},
year = {2026},
month = aug,
doi = {10.1002/pro.70745},
url = {https://hal.science/hal-05777484v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Total synthesis and structural characterization of a novel protein scaffold from the snail Biomphalaria glabrata
AU - Oleg Melnyk
AU - Stéphanie Caby
AU - Armelle Vigouroux
AU - Christine Demanche
AU - Rémi Desmet
AU - Magalie Sénéchal
AU - Benoît Snella
AU - Alexandra Mougel
AU - Céline Boidin‐wichlacz
AU - Aurélie Parmentier
AU - Ugo Pasco
AU - Sonia Cantel
AU - Solange Moréra
AU - Jérôme Vicogne
PY - 2026
DA - 2026/08/05
JO - Protein Science
DO - 10.1002/pro.70745
UR - https://hal.science/hal-05777484v1
AB - Disulfide-rich miniproteins constitute compact and highly stable scaffolds of growing interest for molecular and structural engineering. Schistosomins are $80-residue proteins conserved across gastropods that form a longstanding orphan family whose structure and biological roles have remained unknown. Here, we report the total chemical synthesis and structural characterization of a schistosomin isoform from Biomphalaria glabrata, a medically relevant intermediate host of the parasite Schistosoma mansoni. Using state-of-the-art solid-phase peptide synthesis, chemoselective peptide ligation, and controlled oxidative folding, we obtained homogeneous, wellfolded schistosomin suitable for biophysical and structural studies. High-resolution X-ray crystallography reveals a previously undescribed disulfide-rich fold defining a new class of miniprotein scaffold. Nano differential scanning fluorimetry and circular dichroism experiments demonstrate the remarkable thermal stability of this scaffold. Complementary in silico analyses suggest that the two naturally occurring isoforms, which differ by a single residue, exhibit highly similar structural and dynamic properties. Finally, transcript and protein analyses across snail tissues provide the first spatial expression map of schistosomin in a medically relevant mollusk. Together, this work establishes schistosomin as a novel and robust miniprotein scaffold and provides a structural and biological framework for exploring its function and potential applications.
SN - 0961-8368
SN - 1469-896X
ER -