Structural analysis of neurofibromin by crosslinking mass spectrometry

Neurofibromin (NF1) is a fundamental inhibitor of cell growth that is conserved from yeast to humans. NF1 negatively regulates oncogenic RAS proteins by accelerating the hydrolysis of RAS-bound GTP. This activity blocks growth factor signalling upstream of both mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways. However, the structure and regulatory mechanisms of NF1 have remained elusive. Here we report crosslinking mass spectrometry analysis of the 320 kDa NF1 protein.