1x7s
From Proteopedia
(New page: 200px<br /> <applet load="1x7s" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x7s, resolution 1.55Å" /> '''The X-ray crystallo...) |
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| - | [[Image:1x7s.gif|left|200px]]<br /> | + | [[Image:1x7s.gif|left|200px]]<br /><applet load="1x7s" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1x7s, resolution 1.55Å" /> | caption="1x7s, resolution 1.55Å" /> | ||
'''The X-ray crystallographic structure of the amyloidogenic variant TTR Tyr78Phe'''<br /> | '''The X-ray crystallographic structure of the amyloidogenic variant TTR Tyr78Phe'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Transthyretin (TTR) is a homotetrameric plasma protein that, as a result | + | Transthyretin (TTR) is a homotetrameric plasma protein that, as a result of a set of not yet fully characterized conformational changes, forms fibrillar aggregates that are the major protein component of amyloid deposits. More than 80 mutations associated with TTR amyloid deposition have been described in the literature. X-ray crystallography was used to elucidate the three-dimensional structure of two important TTR variants: TTR Y78F, an amyloidogenic protein, and TTR R104H, which is associated with a protective effect over the amyloidogenic V30M mutation. The structures of those two TTR variants have been determined in space group P2(1)2(1)2 to 1.55 and 1.60 angstroms resolution, respectively, using molecular-replacement techniques. Detailed analysis of the protein model for TTR Y78F indicates a destabilization of the contacts between the alpha-helix and AB loop and the body of the molecule, intimately related to the amyloidogenic nature; contrastingly, in the TTR R104H variant new contacts involving the N-terminal region and His104 are clearly antagonists of amyloid formation. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1X7S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1X7S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X7S OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Damas, A | + | [[Category: Damas, A M.]] |
[[Category: Macedo-Ribeiro, S.]] | [[Category: Macedo-Ribeiro, S.]] | ||
| - | [[Category: Neto-Silva, R | + | [[Category: Neto-Silva, R M.]] |
| - | [[Category: Pereira, P | + | [[Category: Pereira, P J.B.]] |
| - | [[Category: Saraiva, M | + | [[Category: Saraiva, M J.]] |
[[Category: amyloid]] | [[Category: amyloid]] | ||
[[Category: familial amyoidotic polyneuropathy]] | [[Category: familial amyoidotic polyneuropathy]] | ||
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[[Category: x-ray crystallography]] | [[Category: x-ray crystallography]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:51:52 2008'' |
Revision as of 13:51, 21 February 2008
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The X-ray crystallographic structure of the amyloidogenic variant TTR Tyr78Phe
Contents |
Overview
Transthyretin (TTR) is a homotetrameric plasma protein that, as a result of a set of not yet fully characterized conformational changes, forms fibrillar aggregates that are the major protein component of amyloid deposits. More than 80 mutations associated with TTR amyloid deposition have been described in the literature. X-ray crystallography was used to elucidate the three-dimensional structure of two important TTR variants: TTR Y78F, an amyloidogenic protein, and TTR R104H, which is associated with a protective effect over the amyloidogenic V30M mutation. The structures of those two TTR variants have been determined in space group P2(1)2(1)2 to 1.55 and 1.60 angstroms resolution, respectively, using molecular-replacement techniques. Detailed analysis of the protein model for TTR Y78F indicates a destabilization of the contacts between the alpha-helix and AB loop and the body of the molecule, intimately related to the amyloidogenic nature; contrastingly, in the TTR R104H variant new contacts involving the N-terminal region and His104 are clearly antagonists of amyloid formation.
Disease
Known diseases associated with this structure: Amyloid neuropathy, familial, several allelic types OMIM:[176300], Amyloidosis, senile systemic OMIM:[176300], Carpal tunnel syndrome, familial OMIM:[176300], Dystransthyretinemic hyperthyroxinemia OMIM:[176300]
About this Structure
1X7S is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
X-ray crystallographic studies of two transthyretin variants: further insights into amyloidogenesis., Neto-Silva RM, Macedo-Ribeiro S, Pereira PJ, Coll M, Saraiva MJ, Damas AM, Acta Crystallogr D Biol Crystallogr. 2005 Mar;61(Pt 3):333-9. Epub 2005, Feb 24. PMID:15735344
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