Biology subjects

Maita, N.

Publications and source records attributed to Maita, N..

3 recordsLinked to original sources

bioRxiv2026

Organelle-Specific pH Quantification Using a Protein-Based Quantum Sensor

Quantum sensing enables measurements of physicochemical changes within living cells at the organelle level. Conventional nanoparticle-based sensors, however, face limitations in subcellular targeting, intracellular tracking, and following dynamic biological processes across distinct intracellular environments. Here, we investigate MagLOV2, a genetically encoded quantum sensor, by examining its organelle-specific localization, magnetic field effects (MFEs) during mitophagy, and pH dependent response kinetics. MagLOV2 retained magnetic responsiveness in the cytoplasm, nucleus, and mitochondria, with fluorescence contrasts of 17.1%, 12.3%, and 28.0%, respectively. Optimization of mitochondrial targeting increased fluorescence 2.7 fold. During CCCP induced mitophagy, lysosomal colocalization of MagLOV2 increased from 20.75% to 89.73%, accompanied by slower MFE responses in acidic compartments. Purified MagLOV2 showed response times ranging from 8.27 s at pH 4.5 to 1.56 s at pH 9.5. Structural, spectral, and kinetic analyses suggested that protonation dependent flavin photochemistry and the surrounding protein environment contribute to this behavior. These measurements demonstrate that genetically targeted MagLOV2 can follow organelle transport and report local acidification through changes in magnetic-response kinetics.

biophysics↗

bioRxiv2026

ALS-associated mutations reveal a conserved C-terminal self-assembly module in the TDP-43 low-complexity domain

TAR DNA-binding protein 43 (TDP-43) is an RNA-binding protein whose low-complexity domain (LCD) mediates self-assembly, liquid-liquid phase separation, and pathological aggregation associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Previous studies have established the central ultraconserved region (UCR) of the LCD as a major determinant of TDP-43 self-association. However, the contribution of the evolutionarily conserved C-terminal region remains poorly understood. To identify LCD residues required for self-assembly, we systematically analyzed 47 ALS-associated substitutions distributed throughout the TDP-43 LCD using hydrogel-binding and thioflavin T (ThT) assays. Several ALS-associated substitutions within the C-terminal conserved region (CCR) markedly reduced hydrogel incorporation and impaired fibrillization. Similar assembly defects were observed for methionine-to-serine substitutions at two conserved CCR residues, M405 and M414. Furthermore, CCR-containing C-terminal fragments encompassing residues 360-414 or 379-414 formed ThT-positive fibrillar assemblies in vitro. The assembly kinetics exhibited a characteristic lag phase followed by rapid fluorescence growth, consistent with the formation of cross-{beta}-rich assemblies. These findings identify the CCR as an additional conserved self-assembly module within the TDP-43 LCD and expand the prevailing UCR-centered model of TDP-43 assembly. The observation that multiple ALS-associated substitutions reduce rather than enhance self-association further raises the possibility that disruption of normal TDP-43 assembly contributes to disease pathogenesis.

biochemistry↗

bioRxiv2020

Cystal structure of inhibitor-bound human MSPL/TMPRSS13 that can activate high pathogenic avian influenza

Infection of certain influenza viruses is triggered when its hemagglutinin (HA) is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, while the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R{downarrow} sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal -helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19.

biophysics↗