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Structural basis of neurofibromin tetramerization and dimer-tetramer equilibrium

Si, S.; Tueting, C.; Lohse, S.; Landfester, K.; Lieberwirth, I.; Kastritis, P. L.; Harder, A.

2025-02-16 molecular biology
10.1101/2025.02.13.638105 bioRxiv
Show abstract

Human neurofibromin (NF1) is a tumor suppressor multidomain protein known to regulate cellular functions as a dimer. Using cryo-EM, we discovered that neurofibromin can form more highly organized structures and describe tetramerization and a dynamic dimer-to-tetramer equilibrium with extensive interlocked interfaces as well as structural flexibility. The new tetramer structure generates and modifies interaction surfaces and controls protein functions such as microtubule recruitment, thereby providing novel insights into cellular functions.

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