Quasi-continuous cotranslational compaction and folding of a multidomain protein.

Cotranslational folding of a 550-residue multidomain protein occurs through a series of compaction steps, with a key high-force event at RF-2 domain formation.

• Why it matters: Understanding how large, complex proteins fold during synthesis is crucial, as most prior studies focused on small, single-domain proteins, leaving a gap in knowledge about multidomain folding mechanisms.
• What they did: Force Profile Analysis was used to monitor the cotranslational folding of Firefly Luciferase, revealing a quasi-continuous process with intermediate forces and a prominent high-force folding event for RF-2.
• The result: This detailed insight into multidomain cotranslational folding highlights a complex, stepwise process, enabling better understanding of protein biogenesis and potential implications for folding-related diseases.