Santos, L. M. | bioRxiv Science

bioRxiv2025

PRIorI: a graph-based mining of structural arrangements in protein-protein interfaces

SummaryProtein-protein interactions (PPIs) are fundamental to biological processes and central to understanding disease mechanisms, making them essential for drug discovery, peptide-based therapeutics, and vaccine development. Identifying conserved structural arrangements within PPI interfaces can provide valuable insights into molecular recognition and interaction mechanisms. Here, we introduce PRIorI (PRotein-PRotein InteractiOn gRaph Isomorphism), a web-based platform to explore precomputed protein-protein interaction networks and identify conserved atomic-level interaction motifs within structural complexes. Unlike traditional methods, PRIorI models PPI interfaces as bipartite graphs, applying graph isomorphism techniques to efficiently retrieve interaction patterns independent of sequence alignment or structural superimposition. Users can query precomputed PDB interaction graphs, upload custom protein structures, or design structural motifs for targeted searches. To illustrate its applicability, we used PRIorI to analyze the SARS-CoV-2 Spike-ACE2 interface, identifying key interaction motifs previously reported in the literature. The platform successfully identified salt bridges, hydrogen bonds, and hydrophobic interactions that stabilize the viral-host complex, demonstrating PRIorIs utility in protein interaction analysis. Availability and implementationWebserver implemented using typescript, python, Next.js and Express.js. Uses MongoDB for storage, Redis for cache and is hosted by Apache on an Ubuntu Server. PRIorI web platform is freely available at https://priori.ufv.br/. Contactsabrina@ufv.br Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2019

Mps1 releases Mad1 from nuclear pores to ensure a robust mitotic checkpoint and accurate chromosome segregation

The strength of the Spindle Assembly Checkpoint (SAC) depends on the amount of the Mad1-C-Mad2 heterotetramer at kinetochores but also on its binding to Megator/Tpr at nuclear pore complexes (NPCs) during interphase. However, the molecular underpinnings controlling the spatiotemporal redistribution of Mad1-C-Mad2 as cells progress into mitosis remain elusive. Here, we show that Mps1-mediated phosphorylation of Megator/Tpr abolishes its interaction with Mad1 in vitro and in Drosophila cells. Timely activation of Mps1 during prophase triggers Mad1 release from NPCs, which we find to be required for competent kinetochore recruitment of Mad1-C-Mad2 and robust checkpoint response. Importantly, preventing Mad1 binding to Megator/Tpr rescues the fidelity of chromosome segregation and aneuploidy in larval neuroblasts of Drosophila mps1-null mutants. Our findings demonstrate that the subcellular localization of Mad1 is stringently coordinated with cell cycle progression by kinetochore-extrinsic activity of Mps1. This ensures that both NPCs in interphase and kinetochores in mitosis can generate anaphase inhibitors to efficiently preserve genomic stability.

cell biology↗