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Rodrigues, C. D.

Publications and source records attributed to Rodrigues, C. D..

2 recordsLinked to original sources

Assembly of the essential SpoIVA coat protein at the surface of developing bacterial spores

Bacterial spores owe their remarkable resistance properties to a multilayered coat, one of the most resilient and durable biological structures on Earth. Assembled at the surface of the outer forespore membrane, the coat comprises dozens of proteins organized into distinct layers. Its formation is initiated by SpoIVA, which is proposed to form a polymeric scaffold for the innermost coat layer. Although SpoIVA has been shown to polymerize into filaments in vitro, there is currently no evidence demonstrating the formation of such assemblies in vivo, and the mechanism underlying its oligomerization remains unresolved. In this study, cryo-focused ion beam milling combined with cryo-electron tomography of sporulating Bacillus subtilis cells reveals that the SpoIVA layer consists of polymers that form track-like structures radiating from the mother cell-proximal forespore pole and extending directionally toward the distal pole. Subtomogram averaging further sheds light on their organized architecture, harboring a straight orientation, uniform spacing, and embedding in the outer forespore membrane. These observations also define SpoIVA spatial orientation relative to the outer forespore membrane. Furthermore, AlphaFold3 predictions, combined with biophysical and functional assays, show that SpoIVA dimerizes through its central and C-terminal regions. We further show that dimerization promotes SpoIVA localization around the forespore but is dispensable for polymer formation, which relies on the ATPase domain. Altogether, these findings suggest a dual oligomerization mechanism, in which SpoIVA transitions from dimers to linear track-like polymers, and reveal that these assemblies play critical roles in coat assembly and spore development.

microbiology↗

CoEVFold suite: user friendly pipelines to visually represent protein coevolution

Multiple sequence alignment (MSA) data underlies current principles in protein folding and protein-protein interaction prediction, from which large language models (LLMs) in tandem with protein datasets, can predict protein structure. However, what is missing are user-friendly tools that enable researchers to predict and demonstrate coevolution - the principal input which these MSAs infer. Here we present tools to identify and visualize coevolution, through a pipeline (CoEVFold) that uses basic direct coupling algorithms derived from GREMLIN and alignment of sequences from MMSEQs2. The pipeline generates a visual representation of coevolution for a single protein but can also represent coevolution of homomeric or heteromeric protein complexes, as well as coevolution within protein networks. The input for this pipeline can be an amino acid sequence, or user input protein structures from Alphafold their own files or the PDB database. In validation of CoEVFolds capabilities, and utilising proteins from known prokaryotic and eukaryotic model systems (Bacillus subtilis, Escherichia coli and Saccharomyces cerevisiae), as well as phage proteins, CoEVFold predicts coevolution between proteins known to interact, proteins known to oligomerise, and coevolution in proteins known to be part of a protein complex. Collectively, these suite of tools, named CoEVFold suite, have broad applicability and provide a useful toolkit to those interested in dissecting protein-protein interactions and networks. AvailabilityThe code is available online at https://colab.research.google.com/drive/1MSSvNTq7KZ4Lr0XTz89vUuK-J3xOTzwS?usp=sharing and Github. https://github.com/MishterBluesky/CoEVFold Supplementary informationSupplementary data is available via Figshare and supplementary materials.

microbiology↗