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The acitivity of ERM proteins is caused by the association of different regions within the protein.
The acitivity of ERM proteins is caused by the association of different regions within the protein.
Intramolecular interactions characterized to date are linking N-terminal sequences of the protein to C-terminal sequences.(Chercher référence, donner plus précis)
Intramolecular interactions characterized to date are linking N-terminal sequences of the protein to C-terminal sequences.(Chercher référence, donner plus précis)
 +
 +
On en parle ici de tout ce qui sera activation : For instance Ser-10 and Ser-518 phosphorylation by PKA and/or PAK
However Merlin-1 has some properties not shared with ERM proteins.
However Merlin-1 has some properties not shared with ERM proteins.
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The overall architecture of merlin is similar to that of ERM proteins. Indeed they have almost the same organization : a FERM domain,a central α-helical rod, but lack a C-terminal actin-binding site<ref>PMID:22012890</ref>.
The overall architecture of merlin is similar to that of ERM proteins. Indeed they have almost the same organization : a FERM domain,a central α-helical rod, but lack a C-terminal actin-binding site<ref>PMID:22012890</ref>.
===CD44===
===CD44===
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CD44 is a cell-surface receptor for hyaluronan (HA a ligand).
+
CD44 is a cell-surface receptor for hyaluronan (HA a ligand). When HA binds to CD44 the complex promotes tumorigenesis it means it promotes tumor invasion and metastasis. Indeed, CD44 is a receptor presents in the TA3 carcinome mammaire cells and Tr6BC1 schwannoma cells and HA allows their growth.
== References ==
== References ==
<references/>
<references/>

Revision as of 18:03, 22 December 2012

Template:Sandbox ESBS 2012


PDB ID 3u8z

Drag the structure with the mouse to rotate
3u8z, resolution 2.64Å ()
Gene: NF2, SCH (Homo sapiens)


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Merlin FERM Domain

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Contents

Introduction

The merlin-1 protein is encoded by the Neurofibromatosis-2(Nf2) gene. Neurofibromatosis type 2 is an inheritable autosomal dominant disorder. Patients develop tumors of the nervous system : meningiomas, schwannomas, neurofibromas.[1] Mutations in the Nf2 gene lead to tumor proliferation as well in humans as in mice. Therefore Merlin-1 is a tumor suppressor protein.

ERM Proteins

The merlin-1 protein belongs to the band 4.1 superfamily of membrane-cytoskeletal linkers [2]. Within this superfamily merlin-1 is closer to ezrin,radixin and moesin (the ERM proteins). ERM proteins link Adhrens Junctions to the actin cytoskeleton,and are able to remodel Adherens Junctions during epithelial morphogenesis. They also maintain the organization of apical surfaces on the plasma membrane [3]. All these proteins have an about 300-residue globular plasma membrane-associated FERM domain(four-point-one ezrin, radixin, moesin).This FERM domain is a highly conserved domain. This domain is divided into three subdomains (F1, F2, and F3). ERM proteins are composed of a FERM domain followed by a long region with a high α-helical propensity and terminating in a C-terminal domain[4]. The acitivity of ERM proteins is caused by the association of different regions within the protein. Intramolecular interactions characterized to date are linking N-terminal sequences of the protein to C-terminal sequences.(Chercher référence, donner plus précis)

On en parle ici de tout ce qui sera activation : For instance Ser-10 and Ser-518 phosphorylation by PKA and/or PAK

However Merlin-1 has some properties not shared with ERM proteins.

Specificity of merlin FERM domain

Structural differences

The overall architecture of merlin is similar to that of ERM proteins. Indeed they have almost the same organization : a FERM domain,a central α-helical rod, but lack a C-terminal actin-binding site[5].

CD44

CD44 is a cell-surface receptor for hyaluronan (HA a ligand). When HA binds to CD44 the complex promotes tumorigenesis it means it promotes tumor invasion and metastasis. Indeed, CD44 is a receptor presents in the TA3 carcinome mammaire cells and Tr6BC1 schwannoma cells and HA allows their growth.

References

  1. ↑ Martuza RL, Eldridge R. Neurofibromatosis 2 (bilateral acoustic neurofibromatosis). N Engl J Med. 1988 Mar 17;318(11):684-8. PMID:3125435 doi:http://dx.doi.org/10.1056/NEJM198803173181106
  2. ↑ Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Kley N, Menon AG, Pulaski K, et al.. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell. 1993 Nov 19;75(4):826. PMID:8242753
  3. ↑ Brault E, Gautreau A, Lamarine M, Callebaut I, Thomas G, Goutebroze L. Normal membrane localization and actin association of the NF2 tumor suppressor protein are dependent on folding of its N-terminal domain. J Cell Sci. 2001 May;114(Pt 10):1901-12. PMID:11329377
  4. ↑ Fehon RG, McClatchey AI, Bretscher A. Organizing the cell cortex: the role of ERM proteins. Nat Rev Mol Cell Biol. 2010 Apr;11(4):276-87. doi: 10.1038/nrm2866. PMID:20308985 doi:10.1038/nrm2866
  5. ↑ Yogesha SD, Sharff AJ, Giovannini M, Bricogne G, Izard T. Unfurling of the band 4.1, ezrin, radixin, moesin (FERM) domain of the merlin tumor suppressor. Protein Sci. 2011 Oct 19. doi: 10.1002/pro.751. PMID:22012890 doi:10.1002/pro.751

External Resources

  • Li Q, Nance MR, Kulikauskas R, Nyberg K, Fehon R, Karplus PA, Bretscher A, Tesmer JJ. Self-masking in an intact ERM-merlin protein: an active role for the central alpha-helical domain. J Mol Biol. 2007 Feb 2;365(5):1446-59. Epub 2006 Oct 26. PMID:17134719 doi:10.1016/j.jmb.2006.10.075
  • Hennigan RF, Moon CA, Parysek LM, Monk KR, Morfini G, Berth S, Brady S, Ratner N. The NF2 tumor suppressor regulates microtubule-based vesicle trafficking via a novel Rac, MLK and p38(SAPK) pathway. Oncogene. 2012 Apr 23. doi: 10.1038/onc.2012.135. PMID:22525268 doi:10.1038/onc.2012.135
  • Sun CX, Robb VA, Gutmann DH. Protein 4.1 tumor suppressors: getting a FERM grip on growth regulation. J Cell Sci. 2002 Nov 1;115(Pt 21):3991-4000. PMID:12356905
  • Johnson KC, Kissil JL, Fry JL, Jacks T. Cellular transformation by a FERM domain mutant of the Nf2 tumor suppressor gene. Oncogene. 2002 Sep 5;21(39):5990-7. PMID:12203111 doi:10.1038/sj.onc.1205693
  • Li Q, Nance MR, Kulikauskas R, Nyberg K, Fehon R, Karplus PA, Bretscher A, Tesmer JJ. Self-masking in an intact ERM-merlin protein: an active role for the central alpha-helical domain. J Mol Biol. 2007 Feb 2;365(5):1446-59. Epub 2006 Oct 26. PMID:17134719 doi:10.1016/j.jmb.2006.10.075
  • Surace EI, Haipek CA, Gutmann DH. Effect of merlin phosphorylation on neurofibromatosis 2 (NF2) gene function. Oncogene. 2004 Jan 15;23(2):580-7. PMID:14724586 doi:10.1038/sj.onc.1207142
  • Mani T, Hennigan RF, Foster LA, Conrady DG, Herr AB, Ip W. FERM domain phosphoinositide binding targets merlin to the membrane and is essential for its growth-suppressive function. Mol Cell Biol. 2011 May;31(10):1983-96. doi: 10.1128/MCB.00609-10. Epub 2011 Mar , 14. PMID:21402777 doi:10.1128/MCB.00609-10
  • Pearson MA, Reczek D, Bretscher A, Karplus PA. Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell. 2000 Apr 28;101(3):259-70. PMID:10847681

Proteopedia Page Contributors and Editors

Xavière Lornage and Kéliann Lesault

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