Merlin

From Proteopedia

spinqualitylabelsall models Mouse merlin FERM domain (grey) complex with HIV-1 Vpr-binding protein C-terminal (gold) (PDB code 3wa0) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Function Merlin (Mer) or Moesin-exrin-radixin-like protein is a unique tumor suppressor that inhibits mitogenic signaling at the membrane-cytoskeleton interface[1]. The FERM domain of Mer regulates cell proliferation in response to adhesive signaling[2]. Disease Neurofibromatosis type 2, characterized by tumors of the nervous system, is the result of loss of the NF2 gene which encodes Mer[3]. Structural highlights The binding of Mer FERM domain to the C-terminal of HIV-1 Vpr-binding protein results in the inhibition of Mer-mediated suppression of tumorigenesis. The interactions between the proteins are formed by the α-helix and a β-sheet of Mer and a mostly β-sheet of HIV-1 Vpr-binding protein[4].

3D Structures of merlin

Updated on 31-October-2021

Merlin FERM domain 1-320

3u8z, 1h4r – hMer – human
6cds – hMer (mutant)
4zrj – hMer + C-terminal domain (mutant)
7lwh – hMer + Lats1 peptide
4zri – hMer + Lats2 peptide
1isn – mMer - mouse
3wa0 – mMer + HIV-1 Vpr-binding protein residues 1417-1506
4p7i – mMer + HIV-1 Vpr-binding protein residues 998-1058
4zrk – mMer + Lats1 peptide
7edr – Mer + C-terminal domain 510-635 – Drosophila melanogaster

References

1. ↑ Chen H, Mei L, Zhou L, Zhang X, Guo C, Li J, Wang H, Zhu Y, Zheng Y, Huang L. Moesin-ezrin-radixin-like protein (merlin) mediates protein interacting with the carboxyl terminus-1 (PICT-1)-induced growth inhibition of glioblastoma cells in the nucleus. Int J Biochem Cell Biol. 2011 Apr;43(4):545-55. doi:, 10.1016/j.biocel.2010.12.011. Epub 2010 Dec 15. PMID:21167305 doi:http://dx.doi.org/10.1016/j.biocel.2010.12.011
2. ↑ Cooper J, Giancotti FG. Molecular insights into NF2/Merlin tumor suppressor function. FEBS Lett. 2014 Aug 19;588(16):2743-52. doi: 10.1016/j.febslet.2014.04.001. Epub , 2014 Apr 12. PMID:24726726 doi:http://dx.doi.org/10.1016/j.febslet.2014.04.001
3. ↑ Morrow KA, Shevde LA. Merlin: the wizard requires protein stability to function as a tumor suppressor. Biochim Biophys Acta. 2012 Dec;1826(2):400-6. doi: 10.1016/j.bbcan.2012.06.005., Epub 2012 Jun 30. PMID:22750751 doi:http://dx.doi.org/10.1016/j.bbcan.2012.06.005
4. ↑ Mori T, Gotoh S, Shirakawa M, Hakoshima T. Structural basis of DDB1-and-Cullin 4-associated Factor 1 (DCAF1) recognition by merlin/NF2 and its implication in tumorigenesis by CD44-mediated inhibition of merlin suppression of DCAF1 function. Genes Cells. 2014 Jun 9. doi: 10.1111/gtc.12161. PMID:24912773 doi:http://dx.doi.org/10.1111/gtc.12161