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Brysbaert, G.

Publications and source records attributed to Brysbaert, G..

4 recordsLinked to original sources

MassiveFold data for CASP16-CAPRI: a systematic massive sampling experiment

Massive sampling with AlphaFold2 has become a widely used approach in protein structure prediction. Here we present the MassiveFold CASP16-CAPRI dataset, a systematic, large-scale sampling of both monomeric and multimeric protein targets. By exploiting maximal parallelization, we produced up to 8,040 models per target and shared them with the community for collaborative selection and scoring. This collective effort minimizes redundant computation and environmental impact, while granting resource-limited groups - especially those focused on scoring - access to high quality structures. In our analysis, we define an interface-difficulty classification based on DockQ metrics, showing that massive sampling yields the greatest gains on most of the challenging interfaces. Crucially, this classification can be predicted from the median ipTM scores of a routine AF2 run, enabling users to selectively deploy massive sampling only when it is most needed. Combined with a reduction of the massive sampling from 8,040 to 2,475 predictions, such targeted strategies dramatically cut computation time and resource use with minimal loss of accuracy. Finally, we underscore the persistent challenge of choosing optimal models from massive sampling datasets, emphasising the need for more robust scoring methods. The MassiveFold datasets, together with AlphaFold ranking scores and CASP and CAPRI assessment metrics, are publicly available at https://github.com/GBLille/CASP16-CAPRI_MassiveFold_Data to accelerate further progress in protein structure prediction and assembly modeling.

bioinformatics↗

PII1/MRC interaction with Starch Synthase 4 (SS4) from Arabidopsis thaliana inhibits SS4 enzymatic activity

Starch is the major energy storage compound in plants. It accumulates in the form of insoluble, partly crystalline granules whose number and shape are specific to each plant species. These characteristics are defined very early in starch biosynthesis, at the initiation stage. Starch biosynthesis initiation is a complex process that relies on the coordinated action of several proteins that interact together in the so-called complex of initiation. Starch Synthase 4 (SS4) is the only initiation protein with enzymatic activity. It catalyzes the formation of glucan primers, which serve as substrates for the enzymatic machinery that synthesizes starch granules. Previous studies have highlighted the importance of interactions between SS4 and regulatory proteins in this process. Among them, Protein Involved in Initiation 1 (PII1) interacts with SS4 but its function is not yet established. In this study, we explored the structural and functional implications of PII1 on SS4s enzymatic activity. Our findings reveal that PII1 contains a long coiled-coil domain that specifically interacts with SS4, leading to significant inhibition of SS4s glucan elongation activity. Importantly, this inhibition is specific to SS4 and does not affect other known synthases, suggesting a targeted regulatory mechanism. This work describes the structural specificities of PII1 and SS4 and reveals a function for PII1 in the initiation complex. These results allow us to re-examine these complex mechanisms and propose new hypotheses about the important steps in the initiation of starch biosynthesis.

plant biology↗

The "very moment" when UDG recognizes aflipped-out uracil base in dsDNA

Uracil-DNA glycosylase (UDG) is the first enzyme in the base-excision repair (BER) pathway, acting on uracil bases in DNA. How UDG finds its targets has not been conclusively resolved yet. Based on available structural and other experimental evidence, two possible pathways are under discussion. In one, the action of UDG on the DNA bases is believed to follow a pinch-push-pull model, in which UDG generates the base-flip in an active manner. A second scenario is based on the exploitation of bases flipping out thermally from the DNA. Recent molecular dynamics (MD) studies of DNA in trinucleosome arrays have shown that base-flipping can be readily induced by the action of mechanical forces on DNA alone. This alternative mechanism could possibly enhance the probability for the second scnenario of UDG-uracil interaction via the formation of a recognition complex of UDG with flipped-out base. In this work we describe DNA structures with flipped-out uracil bases generated by MD simulations which we then subject to docking simulations with the UDG enzyme. Our results for the UDG-uracil recognition complex support the view that base-flipping induced by DNA mechanics can be a relevant mechanism of uracil base recognition by the UDG glycosylase in chromatin.

bioinformatics↗

Asymmetrical diversification of the receptor-ligand interaction controlling self-incompatibility in Arabidopsis

How two-components genetic systems accumulate evolutionary novelty and become diversified in the course of evolution is a fundamental problem in evolutionary systems biology. In the Brassicaceae, self-incompatibility (SI) is a spectacular example of a diversified allelic series in which numerous highly diverged receptor-ligand combinations are segregating in natural populations. However, the evolutionary mechanisms by which new SI specificities arise in the first place have remained elusive. Using in planta ancestral protein resurrection, we demonstrate that two allelic variants currently segregating as distinct receptor-ligand combinations diverged through an asymmetrical process whereby one variant has retained the same recognition specificity as the (now extinct) ancestor, while the other has functionally diverged and now represents a novel specificity no longer recognized by the ancestor. Examination of the structural determinants of the shift in binding specificity suggests that allosteric changes may be an important source of evolutionary novelty in this highly diversified receptor-ligand system.

evolutionary biology↗