Sandbox Reserved 705: Difference between revisions

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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 name= "utile2" />.

The closed complex of the Merlin proteins corresponds to the tumor suppressor-active form.

'''unlike other ERM head–tail interactions, this structure suggests that binding of the tail provokes dimerization and dynamic movement and unfurling of the F2 motif of the FERM domain. We conclude the “closed” tumor suppressor conformer of merlin-1 is in fact an “open” dimer whose functions are disabled by Nf2 mutations that disrupt this architecture.What triggers sever the supposedly “closed,” tumor suppressor-active form of merlin-1 is less clear, although Ser-10 and Ser-518 phosphorylation by PKA and/or PAK have been proposed to have a role in this response.26,27 Further, phosphomimetic mutants of these sites impair merlin-1 tumor suppression functions and these mutants directly interact with other partners in cells, such as ezrin.28 Binding partners for ERM proteins include each other, and selected adhesion proteins and adapters that direct association with membrane-spanning proteins. For example, the C-terminal domains of the EBP50 and E3KARP members of the NHERF (Na+-H+ Exchanger Regulatory Factor) family bind to ezrin and merlin, and link ERMs to membrane proteins such as NHE3 and CTFR through the agency of their PDZ domains.29 In addition, ERM proteins and merlin also directly bind to adhesion receptors, including NHERF,30 CD44,31 and E-cadherin.7'''<ref name="~~utile~~"/>

'''unlike other ERM head–tail interactions, this structure suggests that binding of the tail provokes dimerization and dynamic movement and unfurling of the F2 motif of the FERM domain. We conclude the “closed” tumor suppressor conformer of merlin-1 is in fact an “open” dimer whose functions are disabled by Nf2 mutations that disrupt this architecture.What triggers sever the supposedly “closed,” tumor suppressor-active form of merlin-1 is less clear, although Ser-10 and Ser-518 phosphorylation by PKA and/or PAK have been proposed to have a role in this response.26,27 Further, phosphomimetic mutants of these sites impair merlin-1 tumor suppression functions and these mutants directly interact with other partners in cells, such as ezrin.28 Binding partners for ERM proteins include each other, and selected adhesion proteins and adapters that direct association with membrane-spanning proteins. For example, the C-terminal domains of the EBP50 and E3KARP members of the NHERF (Na+-H+ Exchanger Regulatory Factor) family bind to ezrin and merlin, and link ERMs to membrane proteins such as NHE3 and CTFR through the agency of their PDZ domains.29 In addition, ERM proteins and merlin also directly bind to adhesion receptors, including NHERF,30 CD44,31 and E-cadherin.7'''<ref name="utile2"/>

Conversely, Merlin's dephosphorylated and closed form is active and functions in tumour suppression and contact inhibition.

Phosphorylation by PAK and PKA at Ser 518 renders the protein inactive in its putatively open form. ERM, Ezrin/Radixin/Moesin; FERM, 4.1 protein/Ezrin/Radixin/Moesin; MYPT1, myosin phosphatase targeting subunit 1; PAK, p21-activated kinase; PKA, protein kinase A; PIP2, phosphatidylinositol 4,5-bisphosphate; RhoK, Ras homologue gene family, member K.

Sandbox Reserved 705: Difference between revisions

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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 name= "utile2" />.
 The closed complex of the Merlin proteins corresponds to the tumor suppressor-active form.
-'''unlike other ERM head–tail interactions, this structure suggests that binding of the tail provokes dimerization and dynamic movement and unfurling of the F2 motif of the FERM domain. We conclude the “closed” tumor suppressor conformer of merlin-1 is in fact an “open” dimer whose functions are disabled by Nf2 mutations that disrupt this architecture.What triggers sever the supposedly “closed,” tumor suppressor-active form of merlin-1 is less clear, although Ser-10 and Ser-518 phosphorylation by PKA and/or PAK have been proposed to have a role in this response.26,27 Further, phosphomimetic mutants of these sites impair merlin-1 tumor suppression functions and these mutants directly interact with other partners in cells, such as ezrin.28 Binding partners for ERM proteins include each other, and selected adhesion proteins and adapters that direct association with membrane-spanning proteins. For example, the C-terminal domains of the EBP50 and E3KARP members of the NHERF (Na+-H+ Exchanger Regulatory Factor) family bind to ezrin and merlin, and link ERMs to membrane proteins such as NHE3 and CTFR through the agency of their PDZ domains.29 In addition, ERM proteins and merlin also directly bind to adhesion receptors, including NHERF,30 CD44,31 and E-cadherin.7'''<ref name="utile"/>
+'''unlike other ERM head–tail interactions, this structure suggests that binding of the tail provokes dimerization and dynamic movement and unfurling of the F2 motif of the FERM domain. We conclude the “closed” tumor suppressor conformer of merlin-1 is in fact an “open” dimer whose functions are disabled by Nf2 mutations that disrupt this architecture.What triggers sever the supposedly “closed,” tumor suppressor-active form of merlin-1 is less clear, although Ser-10 and Ser-518 phosphorylation by PKA and/or PAK have been proposed to have a role in this response.26,27 Further, phosphomimetic mutants of these sites impair merlin-1 tumor suppression functions and these mutants directly interact with other partners in cells, such as ezrin.28 Binding partners for ERM proteins include each other, and selected adhesion proteins and adapters that direct association with membrane-spanning proteins. For example, the C-terminal domains of the EBP50 and E3KARP members of the NHERF (Na+-H+ Exchanger Regulatory Factor) family bind to ezrin and merlin, and link ERMs to membrane proteins such as NHE3 and CTFR through the agency of their PDZ domains.29 In addition, ERM proteins and merlin also directly bind to adhesion receptors, including NHERF,30 CD44,31 and E-cadherin.7'''<ref name="utile2"/>
 Conversely, Merlin's dephosphorylated and closed form is active and functions in tumour suppression and contact inhibition.
   Phosphorylation by PAK and PKA at Ser 518 renders the protein inactive in its putatively open form. ERM, Ezrin/Radixin/Moesin; FERM, 4.1 protein/Ezrin/Radixin/Moesin; MYPT1, myosin phosphatase targeting subunit 1; PAK, p21-activated kinase; PKA, protein kinase A; PIP2, phosphatidylinositol 4,5-bisphosphate; RhoK, Ras homologue gene family, member K.