Rapid Novor Inc

It’s not too late to get all of your hits 🎯

Our new SPR Kinetic Screening service on Biacore 1K is designed to help researchers identify, validate, and rank candidates with greater confidence, while detecting interactions that can be overlooked by less sensitive screening approaches.

𝗪𝗵𝗲𝗻 𝗲𝗮𝗿𝗹𝘆 𝗱𝗶𝘀𝗰𝗼𝘃𝗲𝗿𝘆 𝗱𝗲𝗰𝗶𝘀𝗶𝗼𝗻𝘀 𝗺𝗮𝘁𝘁𝗲𝗿, 𝘀𝘁𝗮𝗿𝘁 𝘄𝗶𝘁𝗵 𝗸𝗶𝗻𝗲𝘁𝗶𝗰 𝗱𝗮𝘁𝗮 𝘆𝗼𝘂 𝗰𝗮𝗻 𝘁𝗿𝘂𝘀𝘁.

Understanding why certain viral mutations become evolutionarily advantageous requires more than static protein structures; it requires studying proteins in motion, in environments that closely resemble their native biological context.

For SARS-CoV-2, much of what we know about the spike protein structure comes from engineered soluble constructs designed for biochemical and structural studies or for vaccines. A recent study by Sophie Shoemaker and colleagues at UC Berkeley and the Gladstone Institute of Virology addresses this gap by combining HDX-MS with enveloped virus-like particles (eVLPs) displaying full-length spike protein in a near-native membrane environment.

💡 𝗞𝗲𝘆 𝗙𝗶𝗻𝗱𝗶𝗻𝗴𝘀 💡
• 𝗩𝗮𝗹𝗶𝗱𝗮𝘁𝗶𝗼𝗻 𝗼𝗳 𝘁𝗵𝗲 𝗼𝗽𝗲𝗻-𝗶𝗻𝘁𝗲𝗿𝗳𝗮𝗰𝗲 𝘁𝗿𝗶𝗺𝗲𝗿 𝗶𝗻 𝗮 𝗻𝗮𝘁𝗶𝘃𝗲 𝗺𝗲𝗺𝗯𝗿𝗮𝗻𝗲 𝗲𝗻𝘃𝗶𝗿𝗼𝗻𝗺𝗲𝗻𝘁: The open-interface trimer was confirmed in membrane-embedded spike, showing that this conformation is an inherent property of the protein rather than an artifact of engineered soluble constructs.
• 𝗧𝗵𝗲 𝗲𝘃𝗼𝗹𝘂𝘁𝗶𝗼𝗻𝗮𝗿𝘆 𝗮𝗱𝘃𝗮𝗻𝘁𝗮𝗴𝗲 𝗼𝗳 𝘁𝗵𝗲 𝗺𝘂𝗹𝘁𝗶𝗯𝗮𝘀𝗶𝗰 𝗳𝘂𝗿𝗶𝗻 𝗰𝗹𝗲𝗮𝘃𝗮𝗴𝗲 𝘀𝗶𝘁𝗲: The additional basic residue in SARS-CoV-2 enhances furin cleavage efficiency. Cleavage at S1/S2 allosterically increases flexibility at the S2′ site, promoting TMPRSS2 processing and membrane fusion, but also favors formation of the open-interface trimer.
• 𝗧𝗵𝗲 𝗲𝘃𝗼𝗹𝘂𝘁𝗶𝗼𝗻𝗮𝗿𝘆 𝗮𝗱𝘃𝗮𝗻𝘁𝗮𝗴𝗲 𝗼𝗳 𝘁𝗵𝗲 𝗗𝟲𝟭𝟰𝗚 𝗺𝘂𝘁𝗮𝘁𝗶𝗼𝗻: D614G stabilizes the closed prefusion trimer, counteracting furin-driven destabilization and reducing premature S1 shedding that could render the virus noninfectious.

HDX-MS is uniquely suited to studies like this because it captures conformational dynamics at peptide resolution without disrupting the native complex. By enabling researchers to probe flexibility, allostery, and transient conformational states, HDX-MS provides insights that static structural techniques alone often cannot capture.

📄𝗥𝗲𝗮𝗱 𝘁𝗵𝗲 𝘀𝘁𝘂𝗱𝘆 𝗵𝗲𝗿𝗲: https://hubs.li/Q04hw9Vn0

🔬𝗟𝗲𝗮𝗿𝗻 𝗺𝗼𝗿𝗲 𝗮𝗯𝗼𝘂𝘁 𝗛𝗗𝗫-𝗠𝗦 𝗵𝗲𝗿𝗲: https://hubs.li/Q04hwbDg0