Department of structural infection biology ([CSSB] STIB)
http://hdl.handle.net/10033/620736
2024-02-19T07:29:35ZFunctional homo- and heterodimeric actin capping proteins from the malaria parasite.
http://hdl.handle.net/10033/623187
Functional homo- and heterodimeric actin capping proteins from the malaria parasite.
Bendes, Ábris Ádám; Chatterjee, Moon; Götte, Benjamin; Kursula, Petri; Kursula, Inari
2020-03-02T00:00:00ZHelical reconstruction of and needle filaments attached to type 3 basal bodies.
http://hdl.handle.net/10033/623059
Helical reconstruction of and needle filaments attached to type 3 basal bodies.
Kotov, Vadim; Lunelli, Michele; Wald, Jiri; Kolbe, Michael; Marlovits, Thomas C
Gram-negative pathogens evolved a syringe-like nanomachine, termed type 3 secretion system, to deliver protein effectors into the cytoplasm of host cells. An essential component of this system is a long helical needle filament that protrudes from the bacterial surface and connects the cytoplasms of the bacterium and the eukaryotic cell. Previous structural research was predominantly focused on reconstituted type 3 needle filaments, which lacked the biological context. In this work we introduce a facile procedure to obtain high-resolution cryo-EM structure of needle filaments attached to the basal body of type 3 secretion systems. We validate our approach by solving the structure of Salmonella PrgI filament and demonstrate its utility by obtaining the first high-resolution cryo-EM reconstruction of Shigella MxiH filament. Our work paves the way to systematic structural characterization of attached type 3 needle filaments in the context of mutagenesis studies, protein structural evolution and drug development.
2021-06-27T00:00:00ZStructural Basis for Designing Multiepitope Vaccines Against COVID-19 Infection: In Silico Vaccine Design and Validation.
http://hdl.handle.net/10033/622852
Structural Basis for Designing Multiepitope Vaccines Against COVID-19 Infection: In Silico Vaccine Design and Validation.
Srivastava, Sukrit; Verma, Sonia; Kamthania, Mohit; Kaur, Rupinder; Badyal, Ruchi Kiran; Saxena, Ajay Kumar; Shin, Ho-Joon; Kolbe, Michael; Pandey, Kailash C
Both designed MEVs are composed of CTL and HTL epitopes screened from 11 Open Reading Frame (ORF), structural and nonstructural proteins of the SARS-CoV-2 proteome. Both MEVs also carry potential B-cell linear and discontinuous epitopes as well as interferon gamma-inducing epitopes. To enhance the immune response of our vaccine design, truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1 was used as an adjuvant at the N termini of both MEVs. The tertiary models for both the designed MEVs were generated, refined, and further analyzed for stable molecular interaction with toll-like receptor 3. Codon-biased complementary DNA (cDNA) was generated for both MEVs and analyzed in silico for high level expression in a mammalian (human) host cell line.
2020-06-19T00:00:00ZNovel Method for Quantifying AhR-Ligand Binding Affinities Using Microscale Thermophoresis.
http://hdl.handle.net/10033/622839
Novel Method for Quantifying AhR-Ligand Binding Affinities Using Microscale Thermophoresis.
Stinn, Anne; Furkert, Jens; Kaufmann, Stefan H E; Moura-Alves, Pedro; Kolbe, Michael
The aryl hydrocarbon receptor (AhR) is a highly conserved cellular sensor of a variety of environmental pollutants and dietary-, cell- and microbiota-derived metabolites with important roles in fundamental biological processes. Deregulation of the AhR pathway is implicated in several diseases, including autoimmune diseases and cancer, rendering AhR a promising target for drug development and host-directed therapy. The pharmacological intervention of AhR processes requires detailed information about the ligand binding properties to allow specific targeting of a particular signaling process without affecting the remaining. Here, we present a novel microscale thermophoresis-based approach to monitoring the binding of purified recombinant human AhR to its natural ligands in a cell-free system. This approach facilitates a precise identification and characterization of unknown AhR ligands and represents a screening strategy for the discovery of potential selective AhR modulators.
2021-02-24T00:00:00Z