Gianlucca Nicastro

[Aravind group @jivarahasya]

Some further press for our recently published paper on the Lipocone superfamily: https://t.co/LGwmORL4Qu

[Aravind group @jivarahasya]

Here is the press release on our recent article describing a novel superfamily of protein domains operating on lipids. Among other things, it unveils the origin of Wnt emerged in animals and numerous other metabolic and biological conflict networks that remain unstudied: https://t.co/JHHTQt2fNZ

[Frederico Gueiros Filho @fredy_gueiros]

My lab and Chuck Farah's at the University of São Paulo (USP) are seeking a postdoc to join an exciting project focused on applying structural biology to novel and unexplored targets in antibiotic discovery.

[Aravind group @jivarahasya]

Extracellular Calcineurin-like phosphoesterases foster and signal altruistic behavior in bacteria

This new work with @RamamurthiLab @ProteinVerse and colleagues uncovers a new role for extracellular calcineurin-like phosphoesterases in bacteria. The calcineurin-like superfamily that originated in some of the earliest reconstructible replicons preceding the last universal common ancestor includes members acting as diverse phosphoesterases: e.g., Calcineurin acts as a protein serine/threonine phosphatase, NadN acts as a NAD + pyrophosphatase; Icc is a cAMP phosphodiesterase; SMPDL3a-like proteins hydrolyze nucleotides such as cytidine 5’-diphosphocholine, cytidine diphosphate ethanolamine and ADP-ribose; the 2’,5’- phosphodiester debranching enzyme is a RNA phosphodiesterase; RNA cyclic 2’-3’ terminus phosphodiesterase acts in RNA repair; SbcD/Mre11 are DNA-recombination exoDNases, while the archaeo-eukaryotic DNA polymerase calcineurin-like subunits are DNA phosphodiesterases acting during replication; yet others were recently predicted by us to act as nucleotide-degrading enzymes in bacterial immunity. However, more mysterious were a large clade of Calcineurin-like enzymes that we describe here: they are extracellular and typically fused to a host of “adhesion” domains like Immunoglobulins, FN3 and the like.
The current work establishes that one such enzyme, ShfP (YvnB) from Bacillus subtilis, generates glycerol, most likely by cleaving it off cell-surface lipoteichoic acids. This glycerol acts both as a signaling molecule and as a nutrient delivered by cells entering sporulation to their nonsporulating kin. The signal is likely received by the histidine kinase KinD via its MCP-N and Cache sensor domains – two domains that we discovered over two decades ago. The work presents evidence that this is a mechanism that fosters phenotypic heterogeneity, resulting in a diverse population that can hedge its bets between a starvation response and a sudden influx of nutrients. Although kin-recognition via conflict systems such as polymorphic toxins are prevalent among microbes, these findings show that genetically encoded modules for cooperative behavior in unicellular organisms can evidently also boost inclusive fitness. https://t.co/kUWsVsaz5N

[Nature Microbiology @NatureMicrobiol]

🦠➗OUT NOW - PcdA promotes division plane selection in #Staph by @RamamurthiLab @felixrl_ @braf_phd @ProteinVerse @Amany_MI @MissiakasLab @cytomotive @jivarahasya @NCIResearchCtr

https://t.co/5DqvKZOgmE

[Kumaran Ramamurthi @RamamurthiLab]

Phenotypic heterogeneity may be ACTIVELY generated (not just passively by stochastic gene expression) in a population of sporulating #Bacillus subtilis, says Updegrove et al.
A new sporulation pathway with 2 proteins of previously unknown function...
https://t.co/KnJNidhOyy

[@[email protected] @KristaTooTurnt]

Baby's first pre-print! The story I've been working on for the past 5 years as a postdoc. In short, I discovered (another) new protein 💅 that catalyzes lipoprotein N-terminal modification, now called Lnb in Bacteroides!

[Sergey Ovchinnikov @sokrypton]

Started teaching again! This time decided to try use #claude (@AnthropicAI) and @codesandbox for hosting to implement an interactive GREMLIN (Potts) model (w = coevolution, b = conservation) to show students how you go from MSA to contacts!

https://t.co/Obfm7BmUe0

[Alex Bisson @Archaeon_Alex]

New paper online @PNASNews! Great collab with @Vikram_Alva, @PohlschroderLab, @SchmidLab and inspiring team work within the Bisson lab.

PNAS: https://t.co/JQ63AmQ8kB

Preprint: https://t.co/QT9EWXA1Sb

Blurb: https://t.co/QYJnOc2D5J

highlights below (1/4)

[Aravind group @jivarahasya]

Growing roles for the NlpC/p60 clade of the Papain-like fold in lipid biochemistry. Nice collaboration with Ethel (@EthelBS) and Robson's (@robfsouza) labs. @ggnicastro

[Ethel Bayer Santos @EthelBS]

Excited to share our latest manuscript in which we analyzed 10,000 Salmonella genomes, identifying 128 T6SS effectors, including 45 new toxin domains (STox). We also characterized STox15, a lipid-targeting NlpC/P60 member.
#Salmonella #T6SS https://t.co/posqHHW1GD

[Aravind group @jivarahasya]

Our new article, “The Prokaryotic Roots of Eukaryotic Immune Systems,” is out. Immune factors from both prokaryotes (e.g., restriction-modification, CRISPR/Cas systems) and eukaryotes (antibodies) have been central reagents for the very emergence of modern biochemistry and molecular biology. But this historical course superficially indicated that the immune systems of prokaryotes and eukaryotes might have little in common. However, starting from our early work on domains involved in eukaryotic apoptosis in the late 1990s, it started becoming increasingly clear to us that there were deep evolutionary connections between eukaryotic and prokaryotic immune systems despite the extreme divergence that is a natural feature of them. These connections take multiple forms: 1. Direct homologies, where immune components were either vertically inherited or laterally transferred from the prokaryotic superkingdoms. This group includes the growing body of evidence regarding domains at the interface of immunity and apoptosis; 2. Then there are homologous domains that were drawn from different prokaryotic conflict systems e.g., those involved in interorganismal conflict and incorporated into eukaryotic immunity – e.g., the mutagenic AID/APOBEC -like deaminases. 3. Finally, there are the analogs that have convergently acquired comparable immune functions in the different superkingdoms. Together they make up a tangled tale of immunity of which we provide a brief account here. You will find little sketches of many domains of interest to the connoisseur and first-time explorer alike: SMODS and friends, TIR, Sirtuin, ADP-ribosyltransferase fold, Schlafen, base deaminases, viperins, caspases, FGS, ricin, GTPases, STANDs, TRADD-N, the Death-like fold and more. https://t.co/dHzdPcP1kX

[Aravind group @jivarahasya]

Coming soon: A "cheatsheat" of some of the widespread anti-invader(e.g., antiviral) molecular immune processes and their sharing across the superkingdoms of Life. Each protein structure is a real rendering of an actual exemplar. The image is divide into three columns representing the three processes -- invader/self–nonself recognition, signaling and effector deployment that can be seen as the overarching operational framework of immune systems.

[Stephen Turner 🦋 @stephenturner.us @strnr]

Multiple Protein Structure Alignment at Scale with FoldMason https://t.co/UwukqANHKI https://t.co/p7qXpi4bnh

[Yunha Hwang @Micro_Yunha]

Introducing the 😱OMG dataset and 🤖gLM2! OMG is a massive Open MetaGenomic corpus totaling 3.1Tbp of data and 3.3B proteins. We train gLM2, the first mixed-modality genomic language model, on OMG. 1/🧵 #BioML #AI4Science

[Aravind group @jivarahasya]

Wolbachia-mediated Cytoplasmic Incompatibility, transposons and other entanglements

Our new collaborative work with @DapengZhang5 lab is out. It investigates the fascinating phenomenon of the genomic basis of Cytoplasmic Incompatibility (CI) and its ultimate origins. This phenomenon is mediated by the endosymbiotic bacterium Wolbachia, which manipulates its host resulting in effects such as feminization, parthenogenesis, male killing, and sperm-egg incompatibility. CI is one such effect of non-Mendelian offspring survivorship from Wolbachia-induced embryonic mortality in the offspring of matings between animals of the same species that differ in their status of Wolbachia infection.

We classify the system involved in this process and show that the primary conserved effector mediating CI is a protein with 4 restriction endonuclease (REase) domains that have their ultimate roots in the REase domains, a group of transposons that spawned CR-effectors of eukaryotes and another mobile element, the Tribolium castaneum Medea1. Remarkably, Medea1’s effector is maternally transmitted via the egg and post-zygotically kills all developing animals that lack at least one copy of the Medea1 locus inherited from their parents in a manner reminiscent of CI. Thus, our studies support a common origin of two distinct non-Mendelian inheritance systems.

We show that in addition to the REase domain, these CI effectors have accreted a wide range of papain-like fold deubiquitinating peptidases (DUBs) from various sources and propose the guardian hypothesis for the original function of these domains in protecting the effector from host Ub-based attacks. Subsequently, in some lineages, these DUBs took on the role of the primary effector. Further, we present evidence for phage/transposon-driven diversification of the CI locus along with the exchange of potential effectors from other gene neighborhoods encoding newly identified effectors potentially mediating other host manipulation actions.

In short, CI has its ultimate roots in bacterial transposons, which on one side, gave rise to these eukaryotic selfish systems and, on another, to antiviral systems, like the STAND NTPases. Remarkably, these domains, whether on a mobile element or an endosymbiotic bacteria genome, have conferred selfish “capture” capacity on the possessor. https://t.co/p6LOMagHSg

[Diorge Souza @diorge_souza]

We're thrilled to share our new preprint: "Evolutionarily Conserved Principles of ESCRT-III-Mediated Membrane Remodeling Revealed by a Two-Subunit Asgard Archaeal System."

https://t.co/1SboXsSj81

[Aravind group @jivarahasya]

Finally our Psp system paper is out: https://t.co/adxHd8lowO
Apart from uncovering manifold ramifications of the Psp system in membrane dynamics going back to the LUCA, it presents some new signaling paradigms: 1. the HAAS-PadR systems as an analogue of 2-component signaling

[Aravind group @jivarahasya]

https://t.co/PVnsyi0cxd Among other things, talks about Reverse transcriptase-based diversifying FGS domain systems that we first identified as key players in bacterial antiviral defense with analogies to animal mutagenesis of antigen receptors.

[Eric Déziel @DezielEric]

New preprint from the lab! @d_oliveirathays noticed that activity of the Pseudomonas aeruginosa quorum sensing regulator RhlR is higher at 25°C than at 37°C, and found indications that such a lower temperature promotes its affinity for its C4-HSL ligand https://t.co/cUMecuU7NE