Biology subjects

Tengganu, I.

Publications and source records attributed to Tengganu, I..

3 recordsLinked to original sources

bioRxiv2026

Proteome-wide crosslinking mass spectrometry reveals novel components of essential complexes in Toxoplasma

Protein-protein interactions underpin nearly all cellular processes, yet systematic definition of these networks remains limited outside a few model organisms. As a result, the architectures of essential complexes in many divergent lineages remain poorly characterized. Here we developed a high-coverage crosslinking mass spectrometry framework to map the proteome-wide interactome of the model apicomplexan parasite Toxoplasma gondii. From 29,624 crosslinked peptide pairs, we resolved a network of 2,859 protein-protein interactions that we integrated with structural modeling to resolve interaction interfaces. We identified and validated previously unrecognized components of essential protein complexes, including a structurally distinct ATP synthase subcomplex containing a highly divergent, apicomplexan-specific subunit essential for parasite fitness. Beyond revealing unexpected diversification of core mitochondrial machinery, these findings provide a general strategy to define the molecular architecture of divergent organisms and represent a foundational resource for hypothesis generation, structural inference, and discovery of lineage-specific vulnerabilities in pathogen biology.

microbiology↗

bioRxiv2025

Transfection of the free-living alga Chromera velia enables direct comparisons with its parasitic apicomplexan relative, Toxoplasma gondii

Chromera velia is a photosynthetic, free-living alga that is closely related to the apicomplexans, a phylum of intracellular parasites responsible for many devastating diseases, including malaria, cryptosporidiosis, and toxoplasmosis. With molecular and cellular landmarks that are clearly related to but distinguishable from those found in apicomplexan parasites, Chromera provides a fantastic opportunity to investigate the evolutionary origin of the structures and processes needed for intracellular parasitism. However, tools for defining localization and functions of gene products do not exist for Chromera, which creates a major bottleneck for exploring its biology. Here we report two major advances in exploring the cell biology of this free-living relative of a large group of intracellular parasites: 1) successful cell transformation and 2) the implementation of expansion microscopy. The initial analysis enabled by these tools generated new insights into subcellular organization in different life stages of Chromera. These new developments boost the potential of Chromera as a model system for understanding the evolution of parasitism in apicomplexans.

cell biology↗

bioRxiv2023

Viral attachment blocking chimera composed of DNAorigami and nanobody inhibits Pseudorabies Virusinfection in vitro

Antivirals are indispensable tools that can be targeted at viral domains directly or indirectly at cellular domains to obstruct viral infections and reduce pathogenicity. Despite their transformative use in healthcare, antivirals have been clinically approved to treat only 10 of the more than 200 known pathogenic human viruses. Additionally, many virus functions are intimately coupled with host cellular processes, which present challenges in antiviral development due to the limited number of clear targets per virus, necessitating an extensive insight into these molecular processes. Compounding this challenge, many viral pathogens have evolved to evade effective antivirals. We hypothesize that a Viral Attachment Blocking Chimera (VirABloC) composed of a viral binder and a bulky scaffold that sterically blocks interactions between a viral particle and a host cell may be suitable for the development of antivirals agnostic to the extravirion epitope that is being bound. We test this hypothesis by modifying a nanobody that specifically recognizes a non-essential epitope presented on the extra virion surface of Pseudorabies virus strain 486 with a 3-dimensional wireframe DNA origami structure [~]100 nm in diameter. The nanobody switches from having no inhibitory properties (tested up to 50 {micro}M) to 4.2 {+/-} 0.9 nM IC50 when conjugated with the DNA origami scaffold. Mechanistic studies support that inhibition is mediated by the non-covalent attachment of the DNA origami scaffold to the virus particle, which obstructs the attachment of the viruses onto host cells. These results support the potential of VirABloC as a generalizable approach to developing antivirals.

biophysics↗