Sandbox Reserved 779: Difference between revisions

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== Overview of Crystalline Structure ==
== Overview of Crystalline Structure ==


βLG consists of 162 amino acid residues (18 kDa), containing two
βLG consists of 162 amino acid residues (18 kDa), containing two disulfide bonds (Cys 66–Cys 160 and Cys 106–Cys 119) and a free thiol
disulfide bonds (Cys 66–Cys 160 and Cys 106–Cys 119) and a free thiol
(Cys 121). Structures of βLG have been reported by several groups with X-ray crystallography [19–21] and solution NMR [29,40,41]
(Cys 121). Structures of βLG have been reported by several groups
(Fig. 1A). It is a predominantly β-sheet protein. The β-barrel, or so called calyx, is conical and is made of two β-sheets: the B–D strands
with X-ray crystallography [19–21] and solution NMR [29,40,41]
and N-terminal half of the A strand (denoted AN) form one sheet, and the E–H strands and C-terminal half of the A strand (denoted AC)
(Fig. 1A). It is a predominantly β-sheet protein. The β-barrel, or socalled
form the other (Fig. 1B). On the outer surface of the β-barrel, between the G and H strands, is the 3-turn α-helix. The loops that
calyx, is conical and is made of two β-sheets: the B–D strands
connect the β-strands at the closed end of the calyx, BC, DE, and FG,are generally quite short, whereas those at the open end, AB, CD, EF,
and N-terminal half of the A strand (denoted AN) form one sheet, and
and GH, are significantly longer and more flexible [19]. In the calyx,there is a large central cavity which is surrounded by hydrophobic
the E–H strands and C-terminal half of the A strand (denoted AC)
residues and is accessible to solvent. This cavity provides the principal ligand-binding site. βLG contains two tryptophan residues,
form the other (Fig. 1B). On the outer surface of the β-barrel,
Trp 19 on the A strand and Trp 61 on the C strand. The former is buried in the hydrophobic core whereas the latter is exposed to the
between the G and H strands, is the 3-turn α-helix. The loops that
solvent in the native structure, making them useful probes for monitoring site-specific conformational changes. In addition, studies
connect the β-strands at the closed end of the calyx, BC, DE, and FG,
on the monomer–dimer equilibrium [30,32,42,43] and the reactivity of the thiol group of Cys121 deeply buried between the α-helix and H
are generally quite short, whereas those at the open end, AB, CD, EF,
and GH, are significantly longer and more flexible [19]. In the calyx,
there is a large central cavity which is surrounded by hydrophobic
residues and is accessible to solvent. This cavity provides the
principal ligand-binding site. βLG contains two tryptophan residues,
Trp 19 on the A strand and Trp 61 on the C strand. The former is
buried in the hydrophobic core whereas the latter is exposed to the
solvent in the native structure, making them useful probes for
monitoring site-specific conformational changes. In addition, studies
on the monomer–dimer equilibrium [30,32,42,43] and the reactivity
of the thiol group of Cys121 deeply buried between the α-helix and H
strand [44–48] revealed other important properties of βLG.
strand [44–48] revealed other important properties of βLG.


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upload the structure (number code:2Q2M)


===secondary structure elements===
===secondary structure elements===
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===Contoh 1===
 
===Protein unfolding===
C-terminal domain<ref name="utile">PMID:20308985</ref>.
C-terminal domain<ref name="utile">PMID:20308985</ref>.
[[Image:imagevraie.gif |thumb|center|650px|Domain organization of ERM<ref name="utile" />]]


[[Image:Cow_milk.jpg |thumb|center|650px|Domain organization of ERM<ref name="utile" />]]
A pathway of sequential unfolding (and folding) of the native 3D structure S0. SU is the coil. The U–ν links in the intermediate Sν keep their native positions and conformations (they are shown as a solid line against the background of a dotted cloud denoting the globule), whereas the other ν links (shown in dashed line) are unfolded.


===Contoh 2===
===Contoh 2===
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and α-helical domains<ref name="utile2">PMID:22012890</ref>.Conformational changes activate the proteins because they modify the intramolecular contacts, allowing them to bind to their partners. The FERM domain has a fundamental role because it allows ERM proteins to interact with integral proteins of the plasma membrane<ref>PMID:12154370</ref>.
and α-helical domains<ref name="utile2">PMID:22012890</ref>.Conformational changes activate the proteins because they modify the intramolecular contacts, allowing them to bind to their partners. The FERM domain has a fundamental role because it allows ERM proteins to interact with integral proteins of the plasma membrane<ref>PMID:12154370</ref>.


[[Image:inactivestate.gif |thumb|left|650px|Inactive ERM protein]][[Image:active2.gif |thumb|right|650px|Active ERM protein]]
[[Image:Cow_milk.jpg |thumb|left|650px|Inactive ERM protein]]
[[Image:Cow_milk.jpg |thumb|right|650px|protein]]






==Specificity of contoh domain==
==Specificity of contoh domain==
{{STRUCTURE_3u8z| PDB=3u8z | SCENE=| size='500'}}
{{STRUCTURE_2q2m| PDB=2q2m | SCENE=| size='400'}}
As showed in the default scene, the structure 3U8Z has in total 4 chains. These are represented by 1 sequence-unique entity. The chains A,B and C possess 9  
As showed in the default scene, the structure 2Q2M has in total 1 Chain. These are represented by 1 sequence-unique entity. The chains A,B and C possess 9  
{{Template:ColorKey_Helix}} and 15 {{Template:ColorKey_Strand}} and the chain D has only 9 {{Template:ColorKey_Helix}}and 14  {{Template:ColorKey_Strand}}. You can visualize their <scene name='Sandbox_Reserved_705/Hidoeurf/1'>repartition</scene>.
{{Template:ColorKey_Helix}} and 15 {{Template:ColorKey_Strand}} and the chain D has only 9 {{Template:ColorKey_Helix}}and 14  {{Template:ColorKey_Strand}}. You can visualize their <scene name='Sandbox_Reserved_705/Hidoeurf/1'>repartition</scene>.


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More precisly,binding of the tail provokes dimerization and unfurling of the F2 motif of the FERM domain.The “closed” complex of merlin-1 is in fact an “open” dimer <ref name="utile" />. For more details about the  probable quaternary states, see the [http://www.ebi.ac.uk/pdbe-srv/view/entry/3u8z/quaternary.html?global_textfield= PDBe page ]about the structure of 3u8z.
More precisly,binding of the tail provokes dimerization and unfurling of the F2 motif of the FERM domain.The “closed” complex of merlin-1 is in fact an “open” dimer <ref name="utile" />. For more details about the  probable quaternary states, see the [http://www.ebi.ac.uk/pdbe-srv/view/entry/3u8z/quaternary.html?global_textfield= PDBe page ]about the structure of 3u8z.


===Merlin regulation===
<scene name='Sandbox_Reserved_705/Jofre/1'>Ser-10</scene> and Ser-518 (not in the FERM domain) phosphorylations by protein kinase A (PKA) and/or p21-activated kinase(PAK) trigger the "closed" complex <ref>PMID:18071304</ref>.
Phosphorylation by PAK and PKA at Ser 518 renders the protein inactive,reducing the inhibition of cell growth.
Merlin possess a serine 10 that can also be phosphorylated by Akt. This phosphorylation directs merlin for proteasome-mediated degradation.<ref>PMID:21750658</ref>. 
Merlin plays a fundamental role in controlling the PI3K/Akt pathway by inhibiting Akt signaling <ref>PMID:15598747</ref>.


Even if the precise mechanism is not known, CD44 is absolutely required for the growth suppressive function
of merlin. The protein interacts with CD44 (a transmembrane protein) but not through the same domain as ERM proteins. This interaction mediates merlin function and is regulated by the concentration of merlin in the cell and also through the concentration of hyaluronate (CD44 ligand). <ref>PMID:11316791</ref>.


===Applications===
===Applications===
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