1fh2
From Proteopedia
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| - | [[Image:1fh2.gif|left|200px]] | + | [[Image:1fh2.gif|left|200px]] |
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| - | '''TRANSTHYRETIN STABILITY AS A KEY FACTOR IN AMYLOIDOGENESIS''' | + | {{Structure |
| + | |PDB= 1fh2 |SIZE=350|CAPTION= <scene name='initialview01'>1fh2</scene>, resolution 1.8Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
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| + | '''TRANSTHYRETIN STABILITY AS A KEY FACTOR IN AMYLOIDOGENESIS''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1FH2 is a [ | + | 1FH2 is a [[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=1FH2 OCA]. |
==Reference== | ==Reference== | ||
| - | Transthyretin stability as a key factor in amyloidogenesis: X-ray analysis at atomic resolution., Sebastiao MP, Lamzin V, Saraiva MJ, Damas AM, J Mol Biol. 2001 Mar 2;306(4):733-44. PMID:[http:// | + | Transthyretin stability as a key factor in amyloidogenesis: X-ray analysis at atomic resolution., Sebastiao MP, Lamzin V, Saraiva MJ, Damas AM, J Mol Biol. 2001 Mar 2;306(4):733-44. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11243784 11243784] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: x-ray crystallography]] | [[Category: x-ray crystallography]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:08:59 2008'' |
Revision as of 09:09, 20 March 2008
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TRANSTHYRETIN STABILITY AS A KEY FACTOR IN AMYLOIDOGENESIS
Contents |
Overview
Transthyretin (TTR) amyloidosis is a conformational disturbance, which, like other amyloidoses, represents a life threat. Here, we report a TTR variant, TTR Thr119Met, that has been shown to have a protective role in the development of clinical symptoms in carriers of TTR Val30Met, one of the most frequent variants among TTR amyloidosis patients. In order to understand this effect, we have determined the structures of the TTR Val30Met/Thr119Met double mutant isolated from the serum of one patient and of both the native and thyroxine complex of TTR Thr119Met. Major conclusions are: (i) new H-bonds within each monomer and monomer-monomer inter-subunit contacts, e.g. Ser117-Ser117 and Met119-Tyr114, increase protein stability, possibly leading to the protective effect of the TTR Val30Met/Thr119Met variant when compared to the single variant TTR Val30Met. (ii) The mutated residue (Met119) extends across the thyroxine binding channel inducing conformational changes that lead to closer contacts between different dimers within the tetramer. The data, at atomic resolution, were essential to detect, for the first time, the subtle changes in the inter-subunit contacts of TTR, and explain the non-amyloidogenic potential of the TTR Thr119Met variant, improving considerably current research on the TTR amyloid fibril formation pathway.
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
1FH2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Transthyretin stability as a key factor in amyloidogenesis: X-ray analysis at atomic resolution., Sebastiao MP, Lamzin V, Saraiva MJ, Damas AM, J Mol Biol. 2001 Mar 2;306(4):733-44. PMID:11243784
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