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1.
PLoS Negl Trop Dis ; 17(9): e0011621, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37656766

RESUMO

Long-term immune evasion by the African trypanosome is achieved through repetitive cycles of surface protein replacement with antigenically distinct versions of the dense Variant Surface Glycoprotein (VSG) coat. Thousands of VSG genes and pseudo-genes exist in the parasite genome that, together with genetic recombination mechanisms, allow for essentially unlimited immune escape from the adaptive immune system of the host. The diversity space of the "VSGnome" at the protein level was thought to be limited to a few related folds whose structures were determined more than 30 years ago. However, recent progress has shown that the VSGs possess significantly more architectural variation than had been appreciated. Here we combine experimental X-ray crystallography (presenting structures of N-terminal domains of coat proteins VSG11, VSG21, VSG545, VSG558, and VSG615) with deep-learning prediction using Alphafold to produce models of hundreds of VSG proteins. We classify the VSGnome into groups based on protein architecture and oligomerization state, contextualize recent bioinformatics clustering schemes, and extensively map VSG-diversity space. We demonstrate that in addition to the structural variability and post-translational modifications observed thus far, VSGs are also characterized by variations in oligomerization state and possess inherent flexibility and alternative conformations, lending additional variability to what is exposed to the immune system. Finally, these additional experimental structures and the hundreds of Alphafold predictions confirm that the molecular surfaces of the VSGs remain distinct from variant to variant, supporting the hypothesis that protein surface diversity is central to the process of antigenic variation used by this organism during infection.


Assuntos
Variação Antigênica , Glicoproteínas de Membrana , Proteínas de Protozoários , Trypanosoma , Proteínas de Membrana
2.
Phys Rev Lett ; 126(20): 203602, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34110198

RESUMO

We study theoretically quantum states of a pair of photons interacting with a finite periodic array of two-level atoms in a waveguide. Our calculation reveals two-polariton eigenstates that have a highly irregular wave function in real space. This indicates the Bethe ansatz breakdown and the onset of quantum chaos, in stark contrast to the conventional integrable problem of two interacting bosons in a box. We identify the long-range waveguide-mediated coupling between the atoms as the key ingredient of chaos and nonintegrability. Our results provide new insights in the interplay between order, chaos, and localization in many-body quantum systems and can be tested in state-of-the-art setups of waveguide quantum electrodynamics.

3.
Phys Rev Lett ; 124(9): 093604, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32202878

RESUMO

We predict the existence of a novel interaction-induced spatial localization in a periodic array of qubits coupled to a waveguide. This localization can be described as a quantum analogue of a self-induced optical lattice between two indistinguishable photons, where one photon creates a standing wave that traps the other photon. The localization is caused by the interplay between on-site repulsion due to the photon blockade and the waveguide-mediated long-range coupling between the qubits.

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