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Scientific result | Structural biology
Thanks to recent developments in cryo-electron microscopy, a study led by a team from the I2BC reveals, at the atomic scale, the unsuspected structural complexity of lanreotide nanotubes, a drug used in the treatment of acromegaly and some neuro-endocrine cancers.
Some peptides have the property of self-assembling and forming "gels" of interest for the formulation of drugs, vaccines or even tissue regeneration. This is the case of lanreotide, a synthetic analogue of somatostatin used as a drug in the treatment of acromegaly and certain neuro-endocrine cancers. The hydrogel that it spontaneously forms in water allows a sustained release formulation (up to one month) of the molecule.
What is its structure? How does it self-assemble? These questions are essential to understand its remarkable properties and to consider the rational design of other self-assembling peptides.
The « Interactions and assembly mechanisms of proteins and peptides » team of the I2BC/CEA-Joliot, in collaboration with researchers from the University of Rennes 1, the SOLEIL synchrotron, the Institut Pasteur and the University of Virginia (USA), have exploited recent developments in cryo-electron microscopy (cryo-EM) to determine, with a resolution of 2.5 Å, the structure of lanreotide nanotubes. This structure is very different from the model proposed more than 20 years ago, based on the structure of a lanreotide monomer.
The study shows once again that higher order assemblies formed by small peptides, even when well characterized, are very difficult to predict.
The results are published in the journal PNAS and were the subject of a communication from the CNRS Institute of Biological Sciences: https://www.insb.cnrs.fr/fr/cnrsinfo/le-fabuleux-monde-nanometrique-des-assemblages-de-peptides-portee-de-vue
Pieri, Fengbin Wang, Ana-Andreea Arteni, Matthijn Vos, Jean-Marie Winter, Marie-Hélène
Le Du, Franck Artzner, Frédéric Gobeaux, Pierre Legrand, Yves Boulard, Stéphane Bressanelli, Edward H. Egelman, Maité Paternostre. Atomic
structure of Lanreotide nanotubes revealed by cryo-EM. | PNAS
January 25, 2022 119 (4) e2120346119
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.