Biology subjects

Mohamed, A. A.

Publications and source records attributed to Mohamed, A. A..

6 recordsLinked to original sources

bioRxiv2026

Structural basis for P-TEFb association with BRD4

Cyclin-dependent kinases (CDK) dynamically regulate RNA Polymerase (Pol) II during each stage of transcription. Phosphorylation of RNA Pol II and associated transcription factors by CDKs enables stage-specific exchange of factors. CDK9 and a cyclin partner (CYCT1, T2 or K) comprise the Positive Transcription Elongation Factor-b (P-TEFb) complex, which is responsible for releasing RNA Pol II from promoter proximal pausing into processive elongation. P-TEFb activity is stimulated by bromodomain-containing Protein 4 (BRD4); however, the structural basis for BRD4 association with P-TEFb has remained unclear. Using cryogenic-electron microscopy, AlphaFold modeling, and biochemical probing, we show that the P-TEFb interacting domain of BRD4 (BRD4-PID) interacts with P-TEFb via the C-lobe of CDK9 and the second cyclin domain of CYCT1. The BRD4 binding surface on CDK9 is also used by super elongation complex component AFF4. Our analysis indicates that BRD4 may stimulate P-TEFb activity by remodeling the kinase C helix relative to previous structures. Finally, P-TEFb activity is restricted when bound to the 7SK RNP complex. We show that in addition to BRD4-PID, the AFF4 N-terminus can release P-TEFb from the 7SK RNP complex. Together, these findings define how P-TEFb activity is regulated by its incorporation into distinct complexes.

biochemistry↗

bioRxiv2026

A biosecurity baseline for transboundary management of marine biological invasions in the ROPME Sea Area

Marine and brackish-water ecosystems are increasingly degraded by cumulative human pressures, with biological invasions representing a major driver of biodiversity loss, ecosystem disruption, and socio-economic impacts. Effective management requires regionally harmonized and scientifically robust baselines capable of supporting coordinated transboundary decision-making. Here we present the first consolidated marine biosecurity baseline for the Regional Organization for the Protection of the Marine Environment (ROPME) Sea Area, a transboundary region characterized by extreme environmental conditions and increasing biosecurity pressure. A total of 192 species (123 extant and 69 horizon), including birds, fishes, tunicates, invertebrates, plants, and chromists, were systematically reviewed, taxonomically validated, and cross-checked against major databases and Member State inputs. Re-evaluation of a previous regional screening revealed substantial inconsistencies, with 24 species ({approx}18%) requiring status correction or exclusion. The resulting consolidated inventory comprised 130 validated retained species supplemented by 62 additional taxa. Extant species were classified according to biogeographic origin and impact status, whereas horizon species were evaluated based on introduction pathways, environmental suitability, and projected climate trends. Risk screening under current and projected climate conditions identified 39 extant species as very high risk, providing an operational basis for progression to full risk assessment and coordinated regional biosecurity management.

ecology↗

bioRxiv2025

RIG-I Stimulation Enhances Effector Function and Proliferation of Primary Human CD8 T Cells

Cytotoxic CD8 T lymphocytes (CTL) are crucial in antiviral immune responses. However, their recruitment to infection sites renders them at risk of viral infection that could modulate their effector activity. CTL express RIG-I that detects cytosolic viral RNA and subsequently induce antiviral gene expression. Here, we investigated how influenza A virus (IAV) infection influence TCR-dependent effector responses. IAV infection of CTL stimulated RIG-I, and activated downstream pathways including TBK1 and NF-B, resulting in type-I interferon secretion. Transfection of CTL with a pure RIG-I ligand, tri-phosphorylated double stranded RNA(3p-dsRNA), not only stimulated these pathways but also enhanced CTL proliferation in vitro and protected them from IAV infection. Analogous with a positive effect on CD8 effector function, both IAV infection and RIG-I ligand transfection enhanced CTL degranulation and cytokine secretion. Conversely, activation of CTL via CD3/CD28-crosslinking increased their susceptibility to IAV infection. Altogether, RIG-I stimulation either by IAV infection or 3p-dsRNA transfection promoted cell intrinsic antiviral pathways and enhanced CD8 effector functions. These findings suggest that RIG-I agonists could enhance and prolong CTL effector function in immunotherapy.

immunology↗

bioRxiv2024

The structural basis for RNA slicing by human Argonaute2

Argonaute (AGO) proteins associate with guide RNAs to form complexes that slice transcripts that pair to the guide. This slicing drives post-transcriptional gene-silencing pathways that are essential for many eukaryotes and the basis for new clinical therapies. Despite this importance, structural information on eukaryotic AGOs in a fully paired, slicing-competent conformation--hypothesized to be intrinsically unstable--has been lacking. Here we present the cryogenic-electron microscopy structure of a human AGO-guide complex bound to a fully paired target, revealing structural rearrangements that enable this conformation. Critically, the N domain of AGO rotates to allow the RNA full access to the central channel and forms contacts that license rapid slicing. Moreover, a conserved loop in the PIWI domain secures the RNA near the active site to enhance slicing rate and specificity. These results explain how AGO accommodates targets possessing the pairing specificity typically observed in biological and clinical slicing substrates.

molecular biology↗

bioRxiv2022

The N-terminal GTPase of Miro1 regulates oligomer formation

The outer-mitochondrial membrane protein Miro1 is critical for the regulation of mitochondrial trafficking. Miro1 contains two GTPase domains, where changes in the N-terminal GTPase nucleotide state strongly affects mitochondrial trafficking. Previous work showed that the GTP-locked mutation Miro1P13V decreases trafficking and affects mitochondrial dynamics. Despite showing a clear role in Miro1 function, the molecular basis for this activity remains unknown. Using in vitro reconstitution, we demonstrate that Miro1 self-associates to form dimers and higher-ordered species. Structural characterization of Miro1P13V suggests that the oligomers adopt a range of conformations in vitro. Additionally, Miro1P13V has diminished interaction with its downstream cargo adapter TRAK1. These results indicate that the NGTPase of Miro1 facilitates the formation of higher-ordered species and suggests that changes in the oligomeric state may regulate mitochondrial trafficking through reduced association with TRAK1.

biochemistry↗

bioRxiv2020

Epitope-Based Peptide Vaccine Design Against Fructose Bisphosphate Aldolase of Candida Glabrata: An Immunomics Approach

Background Candida glabrata is a human opportunistic pathogen that can cause life-threatening systemic infections. Although, there are multiple effective vaccines against fungal infections, and some of these vaccines were engaged in different stages of clinical trials, none of them yet approved by (FDA).Aim To predict the most conserved and immunogenic B- and T-cell epitopes from the Fructose Bisphosphate aldolase (Fba1) protein of C. glabrata.Materials and Methods 13 C. glabrata Fructose bisphosphate aldolase protein sequences (361amino acid) were retrieved from NCBI and several in silico tools presented in the IEDB server for predicting peptides were used and homology modeling and molecular docking were performed.Result The promising B-cell Epitopes were AYFKPH, VDKESLYTK, and HVDKESLYTK. While, promising peptides which have the high affinity to MHC I binding were: AVHEALAPI, KYFKRMAAM, QTSNGGAAY, RMAAMNQWL and YFKEHGEPL. Two peptides (LFSSHMLDL and YIRSIAPAY) were noted to have the highest affinity to MHC class II that interact with 9 MHC class II alleles. The molecular Docking revealed the epitopes QTSNGGAAY and LFSSHMLDL have the high binding energy to MHC moleculesConclusion The epitope-based vaccines predicted by using immunoinformatics tools have remarkable advantages over the conventional vaccines that they are more specific, less time consuming, safe, less allergic and more antigenic. Further in vivo and in vitro experiments are needed to prove the effectiveness of the best candidates epitopes (QTSNGGAAY and LFSSHMLDL). To the best of our knowledge, this is the first study that has predicted B- and T-cells epitopes from Fba1 protein by using in silico tools in order to design an effective epitope-based vaccine against C. galabrata.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioinformatics↗