Inter-domain flexibility in F-Box proteins revealed by integrative modeling

Inter-domain flexibility in F-box proteins is linked to broad conformational sampling in FBXL2 and FBXL17 within assembled SCF and CSN-SCF complexes, unlike FBXL1 and FBXO22.

• Why it matters: Structural studies have defined F-box architecture, but how their domains move and what conformations they can access remains unclear for SCF-mediated substrate recruitment.
• What they did: The team integrated cryo-EM structures, cross-linking mass spectrometry (XL-MS), and deep learning-based conformational ensemble prediction to map accessible conformations across multiple F-box proteins.
• The result: FBXL2 and FBXL17 sampled a broad conformational range in assembled SCF and CSN-SCF complexes, while FBXL1 and FBXO22 showed intrinsic flexibility constrained to a narrower landscape, suggesting tunable plasticity.

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