H2020Индивидуална стипендия2018–2022

CC-LEGO · robust protein blocks to build cages and layers

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-09-01 → 2022-08-31
Финансиране от ЕС: 250 774 €
Участници: 2
Схема: MSCA-IF

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Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

CC-LEGO: robust protein blocks to build cages and layers

The design of new proteins offers significant advantages for human health, such as improved vaccines, drug delivery and novel therapies (e.g. a COVID-19 inhibitor, flu vaccine, treatment of Alzheimer’s). Proteins made of a single polypeptide chain that can take a wide variety of useful shapes can be reliably designed. However, for drug delivery and vaccine applications, larger protein assemblies (including protein cages) are needed. Designing large protein assemblies is difficult, with success rates below ten percent, since atomically accurate interfaces between two protein chains must be designed. The process involves correctly predicting many complex chemical interactions (hydrogen bonding, hydrophobic effect, Van-der-Walls forces, and more). The main aim of the project is to enable easier design of protein cages by circumventing the interface design problem. This is achieved by using existing designed Coiled-Coils (CC) at the cage interface. CCs are some of the best understood protein structures and can be designed with high success rates (>50%). Using sophisticated molecular design software, these CC structures can be rigidly fused to other proteins to form a set of LEGO-like building blocks that can be used to reliably make cages as well as other useful protein nanostructures. A secondary objective is the transfer of knowledge and protein design know-how from a best-in-class protein design institution (the Baker Lab, Washington, USA) to the European Union (National institute of Chemistry, Ljubljana, Slovenia). In conclusion, both objectives have been achieved. We have created pH responsive cages made from rigidly fused building blocks. The Experienced Researcher (Dr. Ljubetič) has learned the computational and experimental side of de novo protein design and has brought the skills and knowledge to the European Union (National institute of Chemistry, Ljubljana, Slovenia), where he is starting up his own group. His career has received a large boost and he has obtained Slovenian funding for his further research.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The design of novel proteins offers unprecedented advantages for human health, such as improved vaccines, drug delivery and novel therapies (e.g. a flu inhibitor, treatment of Alzheimer’s). The state of the art of de novo self-assembling protein nanomaterials is based on the design of protein-protein interfaces. However, due to the complex interplay of numerous weak interactions at the interface the success rate of designed assemblies is currently below 10%. This proposal aims to increase the success rate of designing large protein assemblies, by using coiled-coils (CC) at the interface. CCs are some of the best understood protein motifs and can be designed with high success rates (>50%). A set of well-defined building blocks (CC-LEGOs) will be created by rigidly fusing CC bundles and natural oligomerization domains. Due to precise control of crossing angles enabled by the rigid fusion we expect that CC-LEGO structures will have the high design success rate and high solution homogeneity needed for further applications. A toolbox of CC-LEGO blocks will be designed and experimentally tested, capable of forming cages (tetrahedra, cubes, dodecahedra) as well as open 2D lattices.The experienced researcher (ER) will gain new programming and wet lab skills for protein design through performing world-class research at one of the world’s top universities in a group of a world leader in this field. The expected high impact publications and networking opportunities, coupled with the acquired soft skills in project writing, management, leadership and communication will ensure ER’s competitiveness and enable a successful start of his independent career.Another important impact of the project is the transfer the protein design know-how from the University of Washington to the Slovenian and regional research ecosystem, increasing its excellence. This will be supported by the beneficiary in Slovenia, where most of the wet-lab and computational infrastructure is already in place.

Оригинален текст от CORDIS (на английски).

Участници

KEMIJSKI INSTITUT · LjubljanaКоординаторСловения
UNIVERSITY OF WASHINGTON · Seattle WaСъединени щати