5ttr
From Proteopedia
(New page: 200px<br /> <applet load="5ttr" size="450" color="white" frame="true" align="right" spinBox="true" caption="5ttr, resolution 2.7Å" /> '''LEU 55 PRO TRANSTHYR...) |
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| - | [[Image:5ttr.gif|left|200px]]<br /> | + | [[Image:5ttr.gif|left|200px]]<br /><applet load="5ttr" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="5ttr" size=" | + | |
caption="5ttr, resolution 2.7Å" /> | caption="5ttr, resolution 2.7Å" /> | ||
'''LEU 55 PRO TRANSTHYRETIN CRYSTAL STRUCTURE'''<br /> | '''LEU 55 PRO TRANSTHYRETIN CRYSTAL STRUCTURE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The x-ray crystal structure of the amyloidogenic Leu55 --> Pro | + | The x-ray crystal structure of the amyloidogenic Leu55 --> Pro transthyretin (TTR) variant, implicated as the causative agent in early-onset familial amyloidotic polyneuropathy (Jacobson, D. R., McFarlin, D. E., Kane, I., and Buxbaum, J. N. (1992) Hum. Genet. 89, 353-356), has been solved by molecular replacement, refined at 2.7 A to a Rcryst value of 0.190 (Fobs > 2.0sigma), and compared with wild-type transthyretin to understand the molecular mechanism(s) involved in amyloidogenesis. Leu55 --> Pro TTR crystallizes in space group C2, with eight monomers in the asymmetric unit, and the observed packing contacts are considerably different from those described for the wild-type protein. Refinement of the crystal structure shows that the proline for leucine substitution disrupts the hydrogen bonds between strands D and A, resulting in different interface contacts. Based on the assumption that the observed packing contacts may be significant for amyloidogenesis, a model for the TTR amyloid is proposed. It consists of a tubular structure with inner and outer diameters approximately of 30 and 100 A and four monomers per cross-section. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 5TTR 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:// | + | 5TTR 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=5TTR 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: Saraiva, M | + | [[Category: Saraiva, M J.]] |
| - | [[Category: Sebastiao, M | + | [[Category: Sebastiao, M P.]] |
[[Category: amyloid]] | [[Category: amyloid]] | ||
[[Category: crystal structure]] | [[Category: crystal structure]] | ||
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[[Category: transthyretin]] | [[Category: transthyretin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:15:58 2008'' |
Revision as of 17:15, 21 February 2008
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LEU 55 PRO TRANSTHYRETIN CRYSTAL STRUCTURE
Contents |
Overview
The x-ray crystal structure of the amyloidogenic Leu55 --> Pro transthyretin (TTR) variant, implicated as the causative agent in early-onset familial amyloidotic polyneuropathy (Jacobson, D. R., McFarlin, D. E., Kane, I., and Buxbaum, J. N. (1992) Hum. Genet. 89, 353-356), has been solved by molecular replacement, refined at 2.7 A to a Rcryst value of 0.190 (Fobs > 2.0sigma), and compared with wild-type transthyretin to understand the molecular mechanism(s) involved in amyloidogenesis. Leu55 --> Pro TTR crystallizes in space group C2, with eight monomers in the asymmetric unit, and the observed packing contacts are considerably different from those described for the wild-type protein. Refinement of the crystal structure shows that the proline for leucine substitution disrupts the hydrogen bonds between strands D and A, resulting in different interface contacts. Based on the assumption that the observed packing contacts may be significant for amyloidogenesis, a model for the TTR amyloid is proposed. It consists of a tubular structure with inner and outer diameters approximately of 30 and 100 A and four monomers per cross-section.
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
5TTR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structure of amyloidogenic Leu55 --> Pro transthyretin variant reveals a possible pathway for transthyretin polymerization into amyloid fibrils., Sebastiao MP, Saraiva MJ, Damas AM, J Biol Chem. 1998 Sep 18;273(38):24715-22. PMID:9733771
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