Arturo Carabias

@arturocdr.bsky.social

In this manner, the Fab not only creates steric hindrance during extension, but it likely prevents the initial movements, acting as a lock!. Hence, we named it the “His-Tyr lock” 🔒 (7/9)

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One key contact occurs between H117-Y118 of the antibody heavy chain contact the disulfide bridge C473-C503 of the I-EGF2. This disulfide is the pivoting point between the I-EGF1 and I-EGF2 during αIIbβ3 extension and activation… (6/9)

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Fab 26.4 contacts not only the PSI domain, but also the I-EGF1 and I-EGF2 domains. The interactions with the I-EGF1/2 domains are key to understand how Ab 26.4 prevents integrin activation … (4/9)

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To answer this question, we solved the cryo-EM structure of the Fab fragment of 26.4 bound to αIIbβ3. We found integrin aIIbb3 in the complex is in a bent-closed (i.e. inactive) state. How does the antibody stabilized this inactive conformation? … (3/9)

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Maternal anti-HPA1a antibodies recognize Leu33 in the PSI domain of β3, causing fetal/neonatal alloimmune thrombocytopenia (FNAIT) One such antibody, named 26.4, blocks αIIbβ3 from binding fibrinogen after thrombin stimulation; a key step in clot formation. How does 26.4 bind the integrin?… (2/9)

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++ For a deeper dive into the mechanism, @arturocdr.bsky.social has a fantastic thread, including a beautiful animation of the Retron IX ring! 👇💍🔥 bsky.app/profile/artu...

Arturo Carabias@arturocdr.bsky.social · 3w ago

🧬 Thrilled to share our latest @biorxiv-microbiol.bsky.social preprint! Here we find that Retron-IX build crazy supramolecular rings scaffolded by DNA molecules that sense phage infection! www.biorxiv.org/content/10.6... Read more below🧵! (1/X)

8/10 Why sense B14T? 🤔 Speculation: rec-like nucleases may help phages repair/recombine to escape DNA-targeting immunity. Retron IX could act as a safeguard, detecting phages equipped to evade these defenses. Note it often co-occurs with DNA-targeting systems...

3/10 CryoEM revealed an unexpected supramolecular ring, with HEPN dimers lining its inner rim, held inactive by the DNA-scaffold🔒 I imagine a fleet of "flying saucers" patrolling the cytoplasm, cannons armed & ready to fire... 🛸👽

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🚨 We're hiring! My new lab at EMBL Hamburg is looking for a Research Technician. I'm looking for someone excited by phages, metabolism, enzymes, structural biology and bacterial immunity—if you know the right person, please share this post!🧵⬇️ Apply here: embl.wd103.myworkdayjobs.com/en-US/EMBL/j...

Research Technician (Osterman Group – Metabolism-driven immunity)

EMBL Hamburg / CSSB The European Molecular Biology Laboratory (EMBL) is Europe’s flagship life sciences organization, with more than 110 independent research groups across Heidelberg, Hamburg, Grenobl...

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