Biology subjects

Yamasaki, K.

Publications and source records attributed to Yamasaki, K..

4 recordsLinked to original sources

bioRxiv2025

Structural insights into YheS-mediated release of SecM-arrested ribosome.

ATPase-binding cassette subfamily F (ABCF) proteins interact with the ribosome to resolve translation defects near the peptidyl-transferase center, induced by ribosome-targeting antibiotics or "hard-to-translate" nascent peptides. In Escherichia coli, four ABCF proteins resolve the translation of distinct problematic sequences, but their molecular mechanisms remain unclear. Here, we present a 2.8-[A] cryo-EM structure of the SecM-stalled ribosome in complex with an ATPase-deficient mutant of YheS, an ABCF protein that releases ribosomes stalled during the translation of SecM, a representative ribosome-arresting peptide. YheS is bound to the E-site and relocates the P-site tRNA (P-tRNA) by displacing its CCA-end. Notably, the density of the SecM nascent chain mostly disappeared upon YheS binding. Molecular dynamics simulations support that the P-tRNA relocation generates a pulling force that disrupts key intratunnel interactions essential for arrest. This mechanism is functionally analogous to, yet mechanistically distinct from, the translocon-mediated external pulling force for SecM release. TeaserThe release mechanism of the SecM-arrested ribosome by the ABCF protein YheS was elucidated by structure-based analyses.

biochemistry↗

bioRxiv2020

Elucidation of Japanese pepper (Zanthoxylum piperitum De Candolle) domestication using RAD-Seq

Japanese pepper, Zanthoxylum piperitum, is native to Japan and has four well-known lineages (Asakura, Takahara, Budou, and Arima), which are named after their production area or morphology. Restriction-site associated DNA sequencing (RAD-Seq) was used to analyse 93 accessions from various areas, including these four lineages. Single nucleotide variant analysis was used to classify the plants into eight groups: the Asakura and Arima lineages each had two groups, the Takahara and Budou lineages each had one group, and two additional groups were present. In one Asakura group and two Arima groups, the plants were present in agricultural fields and mountains, thus representing the early stage of domestication of the Japanese pepper. The second Asakura lineage group was closely related to plants present in various areas, and this represents the second stage of domestication of this plant because, after early domestication, genetically related lineages with desirable traits spread to the periphery. These results demonstrate that domestication of Japanese pepper is ongoing. In addition, this study shows that spineless plants are polyphyletic, despite the spineless lineage being considered a subspecies of Japanese pepper.

plant biology↗

bioRxiv2020

Ivermectin reduces coronavirus infection in vivo: a mouse experimental model

SARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus (MHV). BALB/cJ female mice were infected with 6,000 PFU of MHV-A59 (Group Infected; n=20) and immediately treated with one single dose of 500 g/kg of ivermectin (Group Infected + IVM; n=20), or were not infected and treated with PBS (Control group; n=16). Five days after infection/treatment, mice were euthanized to obtain different tissues to check general health status and infection levels. Overall results demonstrated that viral infection induces the typical MHV disease in infected animals, with livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while ivermectin administration showed a better health status with lower viral load (23,192 AU; p<0.05) and few livers with histopathological damage (p<0.05), not showing statistical differences with control mice (P=NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in treated mice compared to infected animals. In conclusion, ivermectin seems to be effective to diminish MHV viral load and disease in mice, being a useful model for further understanding new therapies against coronavirus diseases.

pathology↗

bioRxiv2020

Development of an orally-administrable tumor vasculature-targeting therapeutic using annexin A1-binding D-peptides

IF7 peptide, which binds to the annexin A1 (ANXA1) N-terminal domain, functions as a tumor vasculature-targeted drug delivery vehicle after intravenous injection. To enhance IF7 stability in vivo, we undertook mirror-image peptide phage display using a synthetic D-peptide representing the Anxa1 N-terminus as target. Peptide sequences were identified, synthesized as D-amino acids, and designated as dTIT7, which was shown to bind the ANXA1 N-terminus. Whole body imaging of mouse brain tumors modeled with near infrared fluorescent IRDye-conjugated dTIT7 showed fluorescent signals in brain and kidney. Furthermore, orally-administered geldanamycin (GA)-conjugated dTIT7 suppressed brain tumor growth. Ours is a proof-of-concept experiment showing that Anxa1-binding D-peptide could be developed as an orally-administrable, tumor vasculature-targeted therapeutic. Role of each author: MN designed and performed experiments, analyzed data, and wrote the manuscript; HMA and DLJ produced recombinant ANXA1 protein; KY conducted NMR analysis and data analysis; TOA designed, performed and analyzed LC-MS/MS data; MN, TS, IKT, YS, and TY analyzed peptide-binding assays and performed in silico structural analysis; CTU produced lentivirus for luciferase expression; CNH performed peptide binding assays, tissue culture and animal experiments; and MNF supervised the project and wrote the manuscript.

pharmacology and toxicology↗