Biology subjects

Noor, F.

Publications and source records attributed to Noor, F..

4 recordsLinked to original sources

bioRxiv2025

Proposed mechanism for Rft1-mediated scrambling of a dolichol-linked oligosaccharide

The membrane protein Rft1 is proposed to play an essential role in yeast and human cells by scrambling the glycolipid Man5GlcNAc2-PP-dolichol (M5-DLO) across the endoplasmic reticulum (ER) for protein N-glycosylation. While this activity has been demonstrated in liposomes reconstituted with purified Rft1, biochemical evidence of additional M5-DLO scramblases and the viability of Rft1-null Trypanosoma brucei suggest that scrambling may be a moonlighting function of Rft1 rather than its essential cellular role. To investigate this paradox, we used AlphaFold3 and Chai-1 to model the conformational dynamics of yeast Rft1-M5-DLO complexes. The models suggest an alternating access mechanism, typical of Multidrug/Oligosaccharidyl-lipid/Polysaccharide (MOP) superfamily transporters, in which a cationic central cavity coordinates the anionic headgroup of M5-DLO, while the dolichol tail of the lipid is accommodated through a lateral portal formed by two transmembrane helices. We used the models to design mutations to disrupt the interaction between Rft1 and the M5-DLO headgroup, and to engineer a salt bridge to block the portal and stall transport. Using a Tet-off yeast reporter strain, we tested 26 central cavity mutants and identified two that supported cell growth poorly despite being well-expressed. Strikingly, the portal-blocking mutant which lacks scramblase activity supported robust growth. These data suggest that while M5-DLO binding is important for Rft1s essential function, scrambling activity is dispensable. We propose that Rft1s essential role may be as an M5-DLO chaperone, capturing and routing M5-DLO propitiously on the cytoplasmic side of the ER to coordinate DLO biosynthesis. ImportanceCell surface and secreted proteins are decorated with sugar chains. These chains are first assembled on a lipid carrier. Initial stages of assembly occur on the cytoplasmic side of a subcellular structure called the endoplasmic reticulum (ER). To complete assembly, the partially assembled lipid-linked sugar chain must be flipped across the ER. Here we use computationally guided cell-based assays to examine the role of the Rft1 protein in this process.

biochemistry↗

bioRxiv2025

Inflammatory Biomarkers of Asymptomatic and Symptomatic Tuberculosis

A large proportion of individuals with tuberculosis (TB) are asymptomatic. The biological and inflammatory underpinnings of asymptomatic TB are unknown and may differ from symptomatic TB. We characterised blood transcriptomic and proteomic profiles in South African community screening vs. health facility-based triage cohorts. Asymptomatic TB shared core transcriptomic and proteomic features with symptomatic TB, including upregulation of innate, interferon and inflammatory pathways and downregulation of T and B cell pathways. Integration of transcriptomic and proteomic data from asymptomatic TB individuals identified two distinct sub-clusters characterized by higher or lower bacterial burden, blood IFN-{gamma} responses, BMI, and chest radiographic abnormalities, suggesting different disease severity. We identified a new blood transcriptomic signature of asymptomatic TB. However, diagnostic performance of transcriptomic and proteomic markers was weaker for asymptomatic TB than symptomatic TB, suggesting that policy development for community-based, asymptomatic TB screening should not adopt biomarkers developed for symptomatic TB triage without further optimization.

immunology↗

bioRxiv2025

A single vesicle fluorescence microscopy platform to quantify phospholipid scrambling

Scramblases play important roles in physiology by translocating phospholipids bidirectionally across cell membranes. For example, scrambling facilitated by dimers of the Voltage-Dependent Anion Channel 1 (VDAC1) enables endoplasmic reticulum-derived phospholipids to cross the outer membrane to enter mitochondria. Precise quantification of lipid scrambling, while critical for mechanistic understanding, cannot be obtained from ensemble averaged measurements of reconstituted scramblases. Here, we describe a microscopy platform for high-throughput imaging of single vesicles reconstituted with fluorescently labeled phospholipids and heterogeneously crosslinked VDAC1 dimers. For each vesicle, we quantify size, protein occupancy and scrambling rate. Notably, we find that individual VDAC1 dimers have different activities, ranging from <100 to >10,000 lipids per second. This kinetic heterogeneity, masked in ensemble measurements, reveals that only some dimer interfaces are capable of promoting rapid scrambling, as suggested by molecular dynamics simulations. We extend our analyses to opsin, a monomeric G protein-coupled receptor scramblase, thereby demonstrating the versatility of our platform for quantifying transbilayer lipid transport and exploring its regulation.

biophysics↗

bioRxiv2024

Evolutionary history and rhizosphere microbial community composition in domesticated hops (Humulus lupulus L.)

Humulus lupulus L., commonly known as hops, is a perennial crop grown worldwide and is well known for its pharmacological, commercial, and most importantly brewing applications. For hundreds of years, hops have undergone intense artificial selection with over 250 cultivated varieties being developed worldwide, all displaying differences in key characteristics such as bitter acid concentrations, flavor and aroma profiles, changes in photoperiod, growth, and pathogen/pest resistances. Previous studies have individually explored differences between cultivars, aiming to identify markers that can quickly and cost-effectively differentiate between cultivars. However, little is known about their evolutionary history and the variability in their associated rhizospheric microbial communities. Coupling phenotypic, genomic, and soil metagenomic data, our study aims to explore the global population structure and domestication history of 98 hops cultivars. Additionally, we assessed differences in growth rates, rates of viral infection, usage of dissolvable nitrogen, and soil microbial community compositions between US and non-US based cultivars. Contrary to previous studies, our study revealed that worldwide hop cultivars cluster into four primary subpopulations; Central European, English, and American ancestry as previously reported, and one new group, the Nobles, revealing further substructure amongst Central European cultivars. Modeling the evolutionary history of domesticated hops reveals an early divergence of the common ancestors of modern US cultivars around 2800 ybp, and more recent divergences with gene flow across English, Central European, and Noble cultivars, reconciled with key events in human history and migrations. Furthermore, cultivars of US origin were shown to overall outperform non-US cultivars in both growth rates and usage of dissolvable nitrogen and display novel microbial composition.

evolutionary biology↗