1. Comparative simulative analysis and design of single-chain self-assembled protein cagesFei Xiao, Longfei Luo, Xin Liu, Ajasja Ljubetič, Nengzhi Jin, Roman Jerala, Guang Hu, 2024, original scientific article Abstract: Coiled-coil protein origami (CCPO) is a modular strategy for the de novo design of polypeptide nanostructures. It represents a type of modular design based on pairwise-interacting coiled-coil (CC) units with a single-chain protein programmed to fold into a polyhedral cage. However, the mechanisms underlying the self-assembly of the protein tetrahedron are still not fully understood. In the present study, 18 CCPO cages with three different topologies were modeled in silico. Then, molecular dynamics simulations and CC parameters were calculated to characterize the dynamic properties of protein tetrahedral cages at both the local and global levels. Furthermore, a deformed CC unit was redesigned, and the stability of the new cage was significantly improved.
Keywords: chemical structure, conformation, genetics oligomers stability
Published in DiRROS: 03.10.2024; Views: 100; Downloads: 27
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2. Ultrasound-mediated spatial and temporal control of engineered cells in vivoFilip Ivanovski, Maja Meško, Tina Lebar, Marko Rupnik, Duško Lainšček, Miha Gradišek, Roman Jerala, Mojca Benčina, 2024, original scientific article Published in DiRROS: 09.09.2024; Views: 210; Downloads: 3946
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3. Sequestration of membrane cholesterol by cholesterol-binding proteins inhibits SARS-CoV-2 entry into Vero E6 cellsMagdalena Kulma, Aleksandra Šakanović, Apolonija Bedina Zavec, Simon Caserman, Neža Omersa, Gašper Šolinc, Sara Orehek, Iva Hafner Bratkovič, Urška Kuhar, Brigita Slavec, Uroš Krapež, Matjaž Ocepek, Toshihide Kobayashi, Katarzyna Kwiatkowska, Roman Jerala, Marjetka Podobnik, Gregor Anderluh, 2024, original scientific article Published in DiRROS: 05.08.2024; Views: 258; Downloads: 177
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4. Protein gas vesicles of bacillus megaterium as enhancers of ultrasound-induced transcriptional regulationVid Jazbec, Nina Varda, Ernest Šprager, Maja Meško, Sara Vidmar, Rok Romih, Marjetka Podobnik, Andreja Kežar, Roman Jerala, Mojca Benčina, 2024, original scientific article Published in DiRROS: 01.08.2024; Views: 286; Downloads: 264
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5. Subunits of an E3 ligase complex as degrons for efficient degradation of cytosolic, nuclear, and membrane proteinsAnže Verbič, Tina Lebar, Arne Praznik, Roman Jerala, 2024, original scientific article Keywords: synthetic biology, degrons, control of protein expression, E3 ligase
Published in DiRROS: 05.07.2024; Views: 287; Downloads: 198
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6. TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflamatory consequencesTea Govednik, Duško Lainšček, Urška Kuhar, Marva Lachish, Sandra Janežič, Malan Štrbenc, Uroš Krapež, Roman Jerala, Daphne Atlas, Mateja Manček Keber, 2024, original scientific article Abstract: After three years of the SARS-CoV-2 pandemic, the search and availability of relatively low-cost benchtop therapeutics for people not at high risk for a severe disease are still ongoing. Although vaccines and new SARS-CoV-2 variants reduce the death toll, the long COVID-19 along with neurologic symptoms can develop and persist even after a mild initial infection. Reinfections, which further increase the risk of sequelae in multiple organ systems as well as the risk of death, continue to require caution. The spike protein of SARS-CoV-2 is an important target for both vaccines and therapeutics. The presence of disulfide bonds in the receptor binding domain (RBD) of the spike protein is essential for its binding to the human ACE2 receptor and cell entry. Here, we demonstrate that thiol-reducing peptides based on the active site of oxidoreductase thioredoxin 1, called thioredoxin mimetic (TXM) peptides, can prevent syncytia formation, SARS-CoV-2 entry into cells, and infection in a mouse model. We also show that TXM peptides inhibit the redox-sensitive HIV pseudotyped viral cell entry. These results support disulfide targeting as a common therapeutic strategy for treating infections caused by viruses using redox-sensitive fusion. Furthermore, TXM peptides exert anti-inflammatory properties by lowering the activation of NF-κB and IRF signaling pathways, mitogen-activated protein kinases (MAPKs) and lipopolysaccharide (LPS)-induced cytokines in mice. The antioxidant and anti-inflammatory effects of the TXM peptides, which also cross the blood-brain barrier, in combination with prevention of viral infections, may provide a beneficial clinical strategy to lower viral infections and mitigate severe consequences of COVID-19.
Keywords: SARS-CoV-2, Disulfides, Thiol-reacting compound, Spike, Anti-inflammatory activity
Published in DiRROS: 06.02.2024; Views: 602; Downloads: 243
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8. Development of a simple gelatin-based sensing platform for the sensitive label-free impedimetric detection of SARS-CoV-2Alnilan Cristina Barros Lobato, Maja Šubic, Tea Romih, Lea Žibret, Dino Metarapi, Mojca Benčina, Roman Jerala, Kristijan Vidović, Samo B. Hočevar, Nikola Tasić, 2023, original scientific article Published in DiRROS: 07.08.2023; Views: 736; Downloads: 364
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9. Engineered combinatorial cell device for wound healing and bone regenerationLucija Kadunc, Duško Lainšček, Rok Gašperšič, Petra Sušjan, Uroš Kovačič, Miha Butinar, Boris Turk, Roman Jerala, Iva Hafner Bratkovič, 2023, original scientific article Abstract: Growth factors are the key regulators that promote tissue regeneration and healing processes. While the effects of individual growth factors are well documented, a combination of multiple secreted growth factors underlies stem cell–mediated regeneration. To avoid the potential dangers and laborintensive individual approach of stem cell therapy while maintaining their regeneration-promoting effects based on multiple secreted growth factors, we engineered a “mix-and-match” combinatorial platform based on a library of cell lines producing growth factors. Treatment with a combination of growth factors secreted by engineered mammalian cells was more efficient than with individual growth factors or even stem cell–conditioned medium in a gap closure assay. Furthermore, we implemented in a mouse model a device for allogenic cell therapy for an in situ production of growth factors, where it improved cutaneous wound healing. Augmented bone regeneration was achieved on calvarial bone defects in rats treated with a cell device secreting IGF, FGF, PDGF, TGF-β, and VEGF. In both in vivo models, the systemic concentration of secreted factors was negligible, demonstrating the local effect of the regeneration device. Finally, we introduced a genetic switch that enables temporal control over combinations of trophic factors released at different stages of regeneration mimicking the maturation of natural wound healing to improve therapy and prevent scar formation.
Keywords: wound healing, bone regeneration, growth factors
Published in DiRROS: 01.06.2023; Views: 820; Downloads: 330
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