CryoSHIELDs: tunable amphipathic peptide additives for cryo-EM
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While cryogenic electron microscopy (cryo-EM) has transformed structural biology, sample preparation remains a major determinant of success. Specifically, the air-water interface (AWI) can damage complexes, impose preferred orientation, and reduce particle density. Here, we introduce cryoSHIELDs, a library of peptide additives designed to modulate the AWI and improve cryo-EM grid preparation. Across 24 diverse protein systems, cryoSHIELDs improved particle distribution, angular sampling, complex integrity, and, in selected cases, map quality and resolution. CryoSHIELDs enabled structure determination of the OSMRβ–Vixarelimab complex, the multi-subunit CCAN kinetochore complex without chemical cross-linking, and membrane proteins including ABCC6 and the μ-opioid receptor–Gi complex, the latter resolved at 2.3 Å using tenfold lower protein concentration without compromising map quality. CryoSHIELDs provide a simple, tunable, and broadly applicable platform for more reliable cryo-EM in discovery biology and structure-based drug development.
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CryoSHIELDs: tunable amphipathic peptide additives for cryo-EM www.biorxiv.org/content/10.64898/2026.10.01.755993v1 #cryoEM
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Our latest development is now on bioRxiv: cryoSHIELDs — amphipathic peptide additives that make cryo-EM grid prep far more reliable. Tested across 24 protein systems, they enabled the first ABCC6 structure and GPCR–G protein structures at just 0.1–0.5 mg/mL! www.biorxiv.org/content/10.6...
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CryoSHIELDs: tunable amphipathic peptide additives for cryo-EM https://www.biorxiv.org/content/10.64898/2026.10.01.755993v1
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CryoSHIELDs: tunable amphipathic peptide additives for cryo-EM https://www.biorxiv.org/content/10.64898/2026.10.01.755993v1
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