6CDS

Human neurofibromin 2/merlin/schwannomin residues 1-339 in complex with PIP2

Summary for 6CDS

• Entry DOI: 10.2210/pdb6cds/pdb
• Descriptor: Merlin, [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate, PHOSPHATE ION, ... (6 entities in total)
• Functional Keywords: neurofibromin 2, schwannomin, merlin, tumor suppressor protein, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 82346.45

Authors

Chinthalapudi, K.,Sharff, A.J.,Bricogne, G.,Izard, T. (deposition date: 2018-02-09, release date: 2018-07-18, Last modification date: 2023-10-04)

Primary citation

Chinthalapudi, K.,Mandati, V.,Zheng, J.,Sharff, A.J.,Bricogne, G.,Griffin, P.R.,Kissil, J.,Izard, T.
Lipid binding promotes the open conformation and tumor-suppressive activity of neurofibromin 2.
Nat Commun, 9:1338-1338, 2018

PubMed Abstract: Neurofibromatosis type 2 (NF2) is a tumor-forming disease of the nervous system caused by deletion or by loss-of-function mutations in NF2, encoding the tumor suppressing protein neurofibromin 2 (also known as schwannomin or merlin). Neurofibromin 2 is a member of the ezrin, radixin, moesin (ERM) family of proteins regulating the cytoskeleton and cell signaling. The correlation of the tumor-suppressive function and conformation (open or closed) of neurofibromin 2 has been subject to much speculation, often based on extrapolation from other ERM proteins, and controversy. Here we show that lipid binding results in the open conformation of neurofibromin 2 and that lipid binding is necessary for inhibiting cell proliferation. Collectively, our results provide a mechanism in which the open conformation is unambiguously correlated with lipid binding and localization to the membrane, which are critical for the tumor-suppressive function of neurofibromin 2, thus finally reconciling the long-standing conformation and function debate.

PubMed: 29626191
DOI: 10.1038/s41467-018-03648-4

Experimental method

X-RAY DIFFRACTION (2.62 Å)