Biology subjects

Gonzalez-Rodriguez, N.

Publications and source records attributed to Gonzalez-Rodriguez, N..

3 recordsLinked to original sources

bioRxiv2025

Automated and modular protein binder design with BinderFlow

Deep learning has revolutionised de novo protein design, with new models achieving unprecedented success in creating novel proteins with specific functions, including artificial protein binders. However, current methods remain computationally demanding and challenging to operate without specialised infrastructure and expertise. To overcome these limitations, we developed BinderFlow, a structured and parallelised pipeline for protein binder design. Its batch-basednature enables live monitoring of design campaigns, seamless coexistence with other GPU-intensive processes, and reduces human intervention. Furthermore, BinderFlows modular structure enables straightforward modifications to the design pipeline to incorporate new models and tools or to implement alternative design strategies. Complementing this, we developed BFmonitor, a web-based dashboard that simplifies campaign monitoring, design evaluation, and hit selection. Together, these tools lower the entry barrier for non-specialised users and streamline expert workflows, making generative protein design more accessible, scalable and practical for both exploratory and production-level research.

bioinformatics↗

bioRxiv2024

The yeast CST and Polα/primase complexes act in concert to ensure proper telomere maintenance and protection

Pol/primase, the polymerase that initiates DNA synthesis at replication origins, also completes the task of genome duplication by synthesizing the telomere C-strand under the control of the CST complex. Using cryo-EM structures of the human CST-Pol/primase-DNA complex as guides in conjunction with AlphaFold modeling, we identified structural elements in yeast CST and Pol/primase that promote complex formation. Mutating these structures in Candida glabrata Stn1, Ten1, Pri1 and Pri2 abrogated the stimulatory activity of CST on Pol/primase in vitro, supporting the functional relevance of the physical contacts in cryo-EM structures as well as the conservation of mechanisms between yeast and humans. Introducing these mutations into C. glabrata yielded two distinct groups of mutants. One group exhibited progressive, telomerase-dependent telomere elongation without evidence of DNA damage. The other manifested slow growth, telomere length heterogeneity, ssDNA accumulation and elevated C-circles, which are indicative of telomere deprotection. These telomere deprotection phenotypes are altered or suppressed by mutations in multiple DDR and DNA repair factors. We conclude that in yeast, the telomerase inhibition and telomere protection function previously ascribed to the CST complex are mediated jointly by both CST and Pol/primase, highlighting the critical importance of a replicative DNA polymerase in telomere regulation.

molecular biology↗

bioRxiv2024

Structure of the complete extracellular bacterial flagellum reveals mechanism for flagellin incorporation

The bacterial flagellum is essential for motility, adhesion, and colonization in pathogens like Salmonella enterica and Campylobacter jejuni. Its extracellular structure comprises the hook, hook-filament junction, filament, and filament cap. The native structures of the hook-filament junction and the cap remain elusive, leaving the molecular details of cap-mediated filament assembly largely uncharacterized. Here, we report the structure of the complete extracellular flagellum, encompassing the hook, hook-filament junction, filament, and cap. This structure reveals intermediates of filament assembly, providing a molecular blueprint for flagellin folding and insertion at the filament tip. Mutagenesis and functional assays demonstrate the crucial roles of the caps terminal regions in flagellin incorporation, and of the structural integrity of the hook-filament junction. Finally, the structure of the cap and hook-filament junction prior to filament assembly reveals the structural basis for the initiation of filament assembly. Collectively, this study provides comprehensive insights into flagellum assembly and how flagellin incorporation is coupled with its secretion.

microbiology↗