1iii: Difference between revisions

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[[Image:1iii.gif|left|200px]]<br />

[[Image:1iii.gif|left|200px]]<br /><applet load="1iii" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1iii" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1iii, resolution 2.0Å" />

'''CRYSTAL STRUCTURE OF THE TRANSTHYRETIN MUTANT TTR Y114C-DATA COLLECTED AT ROOM TEMPERATURE'''<br />

==Overview==

The Y114C mutation in human transthyretin (TTR) is associated with a, particular form of familial amyloidotic polyneuropathy. We show that, vitreous aggregates ex vivo consist of either regular amyloid fibrils or, disordered disulfide-linked precipitates that maintain the ability to bind, Congo red. Furthermore, we demonstrate in vitro that the ATTR Y114C mutant, exists in three forms: one unstable but nativelike tetrameric form, one, highly aggregated form in which a network of disulfide bonds is formed, and one fibrillar form. The disulfide-linked aggregates and the fibrillar, form of the mutant can be induced by heat induction under nonreduced and, reduced conditions, respectively. Both forms are recognized by the amyloid, specific antibody MAB(39-44). In a previous study, we have linked exposure, of this epitope in TTR to a three-residue shift in beta-strand D. The, X-ray crystallographic structure of reduced tetrameric ATTR Y114C shows a, structure similar to that of the wild type but with a more buried position, of Cys10 and with beta-mercaptoethanol associated with Cys114, verifying, the strong tendency for this residue to form disulfide bonds. Combined, with the ex vivo data, our in vitro findings suggest that ATTR Y114C can, lead to disease either by forming regular unbranched amyloid fibrils or by, forming disulfide-linked aggregates that maintain amyloid-like properties, but are unable to form regular amyloid fibrils.

The Y114C mutation in human transthyretin (TTR) is associated with a particular form of familial amyloidotic polyneuropathy. We show that vitreous aggregates ex vivo consist of either regular amyloid fibrils or disordered disulfide-linked precipitates that maintain the ability to bind Congo red. Furthermore, we demonstrate in vitro that the ATTR Y114C mutant exists in three forms: one unstable but nativelike tetrameric form, one highly aggregated form in which a network of disulfide bonds is formed, and one fibrillar form. The disulfide-linked aggregates and the fibrillar form of the mutant can be induced by heat induction under nonreduced and reduced conditions, respectively. Both forms are recognized by the amyloid specific antibody MAB(39-44). In a previous study, we have linked exposure of this epitope in TTR to a three-residue shift in beta-strand D. The X-ray crystallographic structure of reduced tetrameric ATTR Y114C shows a structure similar to that of the wild type but with a more buried position of Cys10 and with beta-mercaptoethanol associated with Cys114, verifying the strong tendency for this residue to form disulfide bonds. Combined with the ex vivo data, our in vitro findings suggest that ATTR Y114C can lead to disease either by forming regular unbranched amyloid fibrils or by forming disulfide-linked aggregates that maintain amyloid-like properties but are unable to form regular amyloid fibrils.

==Disease==

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==About this Structure==

1III is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with BME as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1III OCA].

1III is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=BME:'>BME</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1III OCA].

==Reference==

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[[Category: Lundgren, E.]]

[[Category: Olofsson, A.]]

[[Category: Sauer-Eriksson, A.E.]]

[[Category: Sauer-Eriksson, A E.]]

[[Category: BME]]

[[Category: beta barrel]]

[[Category: greek key]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov~~ 12 ~~17:30~~:~~12 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:12:11 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1iii.gif|left|200px]]<br />
+[[Image:1iii.gif|left|200px]]<br /><applet load="1iii" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1iii" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1iii, resolution 2.0&Aring;" />
 '''CRYSTAL STRUCTURE OF THE TRANSTHYRETIN MUTANT TTR Y114C-DATA COLLECTED AT ROOM TEMPERATURE'''<br />
 ==Overview==
-The Y114C mutation in human transthyretin (TTR) is associated with a, particular form of familial amyloidotic polyneuropathy. We show that, vitreous aggregates ex vivo consist of either regular amyloid fibrils or, disordered disulfide-linked precipitates that maintain the ability to bind, Congo red. Furthermore, we demonstrate in vitro that the ATTR Y114C mutant, exists in three forms: one unstable but nativelike tetrameric form, one, highly aggregated form in which a network of disulfide bonds is formed, and one fibrillar form. The disulfide-linked aggregates and the fibrillar, form of the mutant can be induced by heat induction under nonreduced and, reduced conditions, respectively. Both forms are recognized by the amyloid, specific antibody MAB(39-44). In a previous study, we have linked exposure, of this epitope in TTR to a three-residue shift in beta-strand D. The, X-ray crystallographic structure of reduced tetrameric ATTR Y114C shows a, structure similar to that of the wild type but with a more buried position, of Cys10 and with beta-mercaptoethanol associated with Cys114, verifying, the strong tendency for this residue to form disulfide bonds. Combined, with the ex vivo data, our in vitro findings suggest that ATTR Y114C can, lead to disease either by forming regular unbranched amyloid fibrils or by, forming disulfide-linked aggregates that maintain amyloid-like properties, but are unable to form regular amyloid fibrils.
+The Y114C mutation in human transthyretin (TTR) is associated with a particular form of familial amyloidotic polyneuropathy. We show that vitreous aggregates ex vivo consist of either regular amyloid fibrils or disordered disulfide-linked precipitates that maintain the ability to bind Congo red. Furthermore, we demonstrate in vitro that the ATTR Y114C mutant exists in three forms: one unstable but nativelike tetrameric form, one highly aggregated form in which a network of disulfide bonds is formed, and one fibrillar form. The disulfide-linked aggregates and the fibrillar form of the mutant can be induced by heat induction under nonreduced and reduced conditions, respectively. Both forms are recognized by the amyloid specific antibody MAB(39-44). In a previous study, we have linked exposure of this epitope in TTR to a three-residue shift in beta-strand D. The X-ray crystallographic structure of reduced tetrameric ATTR Y114C shows a structure similar to that of the wild type but with a more buried position of Cys10 and with beta-mercaptoethanol associated with Cys114, verifying the strong tendency for this residue to form disulfide bonds. Combined with the ex vivo data, our in vitro findings suggest that ATTR Y114C can lead to disease either by forming regular unbranched amyloid fibrils or by forming disulfide-linked aggregates that maintain amyloid-like properties but are unable to form regular amyloid fibrils.
 ==Disease==
@@ Line 11: / Line 10: @@
 ==About this Structure==
-III is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with BME as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1III OCA].
+III is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=BME:'>BME</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1III OCA].
 ==Reference==
@@ Line 21: / Line 20: @@
 [[Category: Lundgren, E.]]
 [[Category: Olofsson, A.]]
-[[Category: Sauer-Eriksson, A.E.]]
+[[Category: Sauer-Eriksson, A E.]]
 [[Category: BME]]
 [[Category: beta barrel]]
 [[Category: greek key]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:30:12 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:12:11 2008''