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| | {{STRUCTURE_2qpf| PDB=2qpf | SCENE= }} | | {{STRUCTURE_2qpf| PDB=2qpf | SCENE= }} |
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| - | '''Crystal Structure of Mouse Transthyretin'''
| + | ===Crystal Structure of Mouse Transthyretin=== |
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| - | ==Overview==
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| - | The transthyretin amyloidoses appear to be caused by rate-limiting tetramer dissociation and partial monomer unfolding of the human serum protein transthyretin, resulting in aggregation and extracellular deposition of amorphous aggregates and amyloid fibrils. Mice transgenic for few copies of amyloid-prone human transthyretin variants, including the aggressive L55P mutant, failed to develop deposits. Silencing the murine transthyretin gene in the presence of the L55P human gene resulted in enhanced tissue deposition. To test the hypothesis that the murine protein interacted with human transthyretin, preventing the dissociation and partial unfolding required for amyloidogenesis, we produced recombinant murine transthyretin and human/murine transthyretin heterotetramers and compared their structures and biophysical properties to recombinant human transthyretin. We found no significant differences between the crystal structures of murine and human homotetramers. Murine transthyretin is not amyloidogenic because the native homotetramer is kinetically stable under physiologic conditions and cannot dissociate into partially unfolded monomers, the misfolding and aggregation precursor. Heterotetramers composed of murine and human subunits are also kinetically stable. These observations explain the lack of transthyretin deposition in transgenics carrying a low copy number of human transthyretin genes. The incorporation of mouse subunits into tetramers otherwise composed of human amyloid-prone transthyretin subunits imposes kinetic stability, preventing dissociation and subsequent amyloidogenesis. | + | The line below this paragraph, {{ABSTRACT_PUBMED_18006495}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 18006495 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_18006495}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Transport protein]] | | [[Category: Transport protein]] |
| | [[Category: Vitamin some]] | | [[Category: Vitamin some]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 15:22:03 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:16:57 2008'' |
Revision as of 15:17, 27 July 2008
Template:STRUCTURE 2qpf
Crystal Structure of Mouse Transthyretin
Template:ABSTRACT PUBMED 18006495
About this Structure
2QPF is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Human-Murine Transthyretin Heterotetramers Are Kinetically Stable and Non-amyloidogenic: A LESSON IN THE GENERATION OF TRANSGENIC MODELS OF DISEASES INVOLVING OLIGOMERIC PROTEINS., Reixach N, Foss TR, Santelli E, Pascual J, Kelly JW, Buxbaum JN, J Biol Chem. 2008 Jan 25;283(4):2098-107. Epub 2007 Nov 15. PMID:18006495
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