The ERM protein family consists of three closely related proteins, ezrin,[2]radixin[3] and moesin.[4][5] The three paralogs, ezrin, radixin and moesin, are present in vertebrates, whereas other species have only one ERM gene. Therefore, in vertebrates these paralogs likely arose by gene duplication.[6]
ERM proteins are highly conserved throughout evolution. More than 75% identity is observed in the N-terminal and the C-terminal of vertebrates (ezrin, radixin, moesin), Drosophila (dmoesin) and C. elegans (ERM-1) homologs.[7]
ERM molecules contain the following three domains:[5]
N-terminal globular domain, also called FERM domain (Band 4.1, ezrin, radixin, moesin). The FERM domain allows ERM proteins to interact with integral proteins of the plasma membrane, or scaffolding proteins localized beneath the plasma membrane.[6] The FERM domain is composed of three subdomains (F1, F2, F3) that are arranged as a cloverleaf.
charged C-terminal domain. This domain mediates the interaction with F-actin.
Ezrin, radixin and moesin also contain a polyproline region between the central helical and C-terminal domains.
Functionedit
ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament-plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains.[5][8]
The ERM protein moesin directly binds to microtubules via its N-terminal FERM domain in vitro and stabilizes microtubules at the cell cortex in vivo. This interaction is required for specific ERM-dependent functions in mitosis.[9]
Activationedit
ERM proteins are highly regulated proteins. They exist in two forms:[6][7]
the FERM domain is able to interact with the F-actin binding site and this head-to-tail interaction maintains ERM proteins into a folded form; in this state, ERM proteins are inactive for the folding prevents either integral protein binding, or actin-binding.
if this head-to-tail interaction is disrupted, ERM proteins unfold, leading to an open and active conformation.
In culture cells, ERM proteins mainly exhibit the folded conformation (about 80-85%[10]).
The current model for ERM protein activation is a two-step mechanism:[11]
Then, a not yet identified kinase phosphorylates a Threonine localized in a highly conserved region of the C-terminal domain. The phosphate will stabilize the opening of the molecule.
Referencesedit
^PDB: 1E5W; Edwards SD, Keep NH (June 2001). "The 2.7 Å crystal structure of the activated FERM domain of moesin: an analysis of structural changes on activation". Biochemistry. 40 (24): 7061–8. doi:10.1021/bi010419h. PMID 11401550.
^Bretscher A (August 1983). "Purification of an 80,000-dalton protein that is a component of the isolated microvillus cytoskeleton, and its localization in nonmuscle cells". J. Cell Biol. 97 (2): 425–32. doi:10.1083/jcb.97.2.425. PMC2112519. PMID 6885906.
^Tsukita S, Hieda Y, Tsukita S (June 1989). "A new 82-kD barbed end-capping protein (radixin) localized in the cell- to-cell adherens junction: purification and characterization". J. Cell Biol. 108 (6): 2369–82. doi:10.1083/jcb.108.6.2369. PMC2115614. PMID 2500445.
^Lankes W, Griesmacher A, Grünwald J, Schwartz-Albiez R, Keller R (May 1988). "A heparin-binding protein involved in inhibition of smooth-muscle cell proliferation". Biochem. J. 251 (3): 831–42. doi:10.1042/bj2510831. PMC1149078. PMID 3046603.
^ abcBretscher A, Edwards K, Fehon RG (August 2002). "ERM proteins and merlin: integrators at the cell cortex". Nat Rev Mol Cell Biol. 3 (8): 586–99. doi:10.1038/nrm882. PMID 12154370. S2CID 26970178.
^ abFiévet B, Louvard D, Arpin M (May 2007). "ERM proteins in epithelial cell organization and functions". Biochim Biophys Acta. 1773 (5): 653–60. doi:10.1016/j.bbamcr.2006.06.013. PMID 16904765.
^Yonemura S, Hirao M, Doi Y, Takahashi N, Kondo T, Tsukita S, Tsukita S (February 1998). "Ezrin/Radixin/Moesin (ERM) Proteins Bind to a Positively Charged Amino Acid Cluster in the Juxta-Membrane Cytoplasmic Domain of CD44, CD43, and ICAM-2". J. Cell Biol. 140 (4): 885–95. doi:10.1083/jcb.140.4.885. PMC2141743. PMID 9472040.
^Solinet S, Mahmud K, Stewman SF, Ben El Kadhi K, Decelle B, Talje L, Ma A, Kwok BH, Carreno S (July 2013). "The actin-binding ERM protein Moesin binds to and stabilizes microtubules at the cell cortex". J. Cell Biol. 202 (2): 251–60. doi:10.1083/jcb.201304052. PMC3718980. PMID 23857773.
^Gautreau A, Louvard D, Arpin M (July 2000). "Morphogenic Effects of Ezrin Require a Phosphorylation-Induced Transition from Oligomers to Monomers at the Plasma Membrane". J. Cell Biol. 150 (1): 193–203. doi:10.1083/jcb.150.1.193. PMC2185562. PMID 10893267.
^Fievet BT, Gautreau A, Roy C, Del Maestro L, Mangeat P, Louvard D, Arpin M (March 2004). "Phosphoinositide binding and phosphorylation act sequentially in the activation mechanism of ezrin". J. Cell Biol. 164 (5): 653–9. doi:10.1083/jcb.200307032. PMC2172172. PMID 14993232.
December 07, 2023
protein, family, consists, three, closely, related, proteins, ezrin, radixin, moesin, three, paralogs, ezrin, radixin, moesin, present, vertebrates, whereas, other, species, have, only, gene, therefore, vertebrates, these, paralogs, likely, arose, gene, duplic. The ERM protein family consists of three closely related proteins ezrin 2 radixin 3 and moesin 4 5 The three paralogs ezrin radixin and moesin are present in vertebrates whereas other species have only one ERM gene Therefore in vertebrates these paralogs likely arose by gene duplication 6 Ezrin radixin moesin familyCrystallographic structure of the N terminal domain of moesin 1 IdentifiersSymbolERMPfamPF00769InterProIPR011259SCOP21ef1 SCOPe SUPFAMAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryPDB1ef1 1e5w 1sgh ERM proteins are highly conserved throughout evolution More than 75 identity is observed in the N terminal and the C terminal of vertebrates ezrin radixin moesin Drosophila dmoesin and C elegans ERM 1 homologs 7 Contents 1 Structure 2 Function 3 Activation 4 ReferencesStructure editERM molecules contain the following three domains 5 N terminal globular domain also called FERM domain Band 4 1 ezrin radixin moesin The FERM domain allows ERM proteins to interact with integral proteins of the plasma membrane or scaffolding proteins localized beneath the plasma membrane 6 The FERM domain is composed of three subdomains F1 F2 F3 that are arranged as a cloverleaf extended alpha helical domain charged C terminal domain This domain mediates the interaction with F actin Ezrin radixin and moesin also contain a polyproline region between the central helical and C terminal domains Function editERM proteins crosslink actin filaments with plasma membranes They co localize with CD44 at actin filament plasma membrane interaction sites associating with CD44 via their N terminal domains and with actin filaments via their C terminal domains 5 8 The ERM protein moesin directly binds to microtubules via its N terminal FERM domain in vitro and stabilizes microtubules at the cell cortex in vivo This interaction is required for specific ERM dependent functions in mitosis 9 Activation editERM proteins are highly regulated proteins They exist in two forms 6 7 the FERM domain is able to interact with the F actin binding site and this head to tail interaction maintains ERM proteins into a folded form in this state ERM proteins are inactive for the folding prevents either integral protein binding or actin binding if this head to tail interaction is disrupted ERM proteins unfold leading to an open and active conformation In culture cells ERM proteins mainly exhibit the folded conformation about 80 85 10 The current model for ERM protein activation is a two step mechanism 11 First phosphatidylinositol 4 5 bisphosphate interaction at the plasma membrane induces a pre opening of the ERM molecule Then a not yet identified kinase phosphorylates a Threonine localized in a highly conserved region of the C terminal domain The phosphate will stabilize the opening of the molecule References edit PDB 1E5W Edwards SD Keep NH June 2001 The 2 7 A crystal structure of the activated FERM domain of moesin an analysis of structural changes on activation Biochemistry 40 24 7061 8 doi 10 1021 bi010419h PMID 11401550 Bretscher A August 1983 Purification of an 80 000 dalton protein that is a component of the isolated microvillus cytoskeleton and its localization in nonmuscle cells J Cell Biol 97 2 425 32 doi 10 1083 jcb 97 2 425 PMC 2112519 PMID 6885906 Tsukita S Hieda Y Tsukita S June 1989 A new 82 kD barbed end capping protein radixin localized in the cell to cell adherens junction purification and characterization J Cell Biol 108 6 2369 82 doi 10 1083 jcb 108 6 2369 PMC 2115614 PMID 2500445 Lankes W Griesmacher A Grunwald J Schwartz Albiez R Keller R May 1988 A heparin binding protein involved in inhibition of smooth muscle cell proliferation Biochem J 251 3 831 42 doi 10 1042 bj2510831 PMC 1149078 PMID 3046603 a b c Tsukita S Yonemura S Tsukita S February 1997 ERM proteins head to tail regulation of actin plasma membrane interaction Trends Biochem Sci 22 2 53 8 doi 10 1016 S0968 0004 96 10071 2 PMID 9048483 a b c Bretscher A Edwards K Fehon RG August 2002 ERM proteins and merlin integrators at the cell cortex Nat Rev Mol Cell Biol 3 8 586 99 doi 10 1038 nrm882 PMID 12154370 S2CID 26970178 a b Fievet B Louvard D Arpin M May 2007 ERM proteins in epithelial cell organization and functions Biochim Biophys Acta 1773 5 653 60 doi 10 1016 j bbamcr 2006 06 013 PMID 16904765 Yonemura S Hirao M Doi Y Takahashi N Kondo T Tsukita S Tsukita S February 1998 Ezrin Radixin Moesin ERM Proteins Bind to a Positively Charged Amino Acid Cluster in the Juxta Membrane Cytoplasmic Domain of CD44 CD43 and ICAM 2 J Cell Biol 140 4 885 95 doi 10 1083 jcb 140 4 885 PMC 2141743 PMID 9472040 Solinet S Mahmud K Stewman SF Ben El Kadhi K Decelle B Talje L Ma A Kwok BH Carreno S July 2013 The actin binding ERM protein Moesin binds to and stabilizes microtubules at the cell cortex J Cell Biol 202 2 251 60 doi 10 1083 jcb 201304052 PMC 3718980 PMID 23857773 Gautreau A Louvard D Arpin M July 2000 Morphogenic Effects of Ezrin Require a Phosphorylation Induced Transition from Oligomers to Monomers at the Plasma Membrane J Cell Biol 150 1 193 203 doi 10 1083 jcb 150 1 193 PMC 2185562 PMID 10893267 Fievet BT Gautreau A Roy C Del Maestro L Mangeat P Louvard D Arpin M March 2004 Phosphoinositide binding and phosphorylation act sequentially in the activation mechanism of ezrin J Cell Biol 164 5 653 9 doi 10 1083 jcb 200307032 PMC 2172172 PMID 14993232 Retrieved from https en wikipedia org w index php title ERM protein family amp oldid 1165343056, wikipedia, wiki, book, books, library,
