1soq
From Proteopedia
(New page: 200px<br /> <applet load="1soq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1soq, resolution 2.10Å" /> '''Crystal structure o...) |
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| - | [[Image:1soq.gif|left|200px]]<br /> | + | [[Image:1soq.gif|left|200px]]<br /><applet load="1soq" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1soq, resolution 2.10Å" /> | caption="1soq, resolution 2.10Å" /> | ||
'''Crystal structure of the transthyretin mutant A108Y/L110E solved in space group C2'''<br /> | '''Crystal structure of the transthyretin mutant A108Y/L110E solved in space group C2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Conformational changes in native and variant forms of the human plasma | + | Conformational changes in native and variant forms of the human plasma protein transthyretin (TTR) induce several types of amyloid diseases. Biochemical and structural studies have mapped the initiation site of amyloid formation onto residues at the outer C and D beta-strands and their connecting loop. In this study, we characterise an engineered variant of transthyretin, Ala108Tyr/Leu110Glu, which is kinetically and thermodynamically more stable than wild-type transthyretin, and as a consequence less amyloidogenic. Crystal structures of the mutant were determined in two space groups, P2(1)2(1)2 and C2, from crystals grown in the same crystallisation set-up. The structures are identical with the exception for residues Leu55-Leu58, situated at beta-strand D and the following DE loop. In particular, residues Leu55-His56 display large shifts in the C2 structure. There the direct hydrogen bonding between beta-strands D and A has been disrupted and is absent, whereas the beta-strand D is present in the P2(1)2(1)2 structure. This difference shows that from a mixture of metastable TTR molecules, only the molecules with an intact beta-strand D are selected for crystal growth in space group P2(1)2(1)2. The packing of TTR molecules in the C2 crystal form and in the previously determined amyloid TTR (ATTR) Leu55Pro crystal structure is close-to-identical. This packing arrangement is therefore not unique in amyloidogenic mutants of TTR. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1SOQ 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:// | + | 1SOQ 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=1SOQ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Lundgren, E.]] | [[Category: Lundgren, E.]] | ||
[[Category: Olofsson, A.]] | [[Category: Olofsson, A.]] | ||
| - | [[Category: Sauer-Eriksson, A | + | [[Category: Sauer-Eriksson, A E.]] |
[[Category: greek key beta barrel]] | [[Category: greek key beta barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:03:38 2008'' |
Revision as of 13:03, 21 February 2008
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Crystal structure of the transthyretin mutant A108Y/L110E solved in space group C2
Contents |
Overview
Conformational changes in native and variant forms of the human plasma protein transthyretin (TTR) induce several types of amyloid diseases. Biochemical and structural studies have mapped the initiation site of amyloid formation onto residues at the outer C and D beta-strands and their connecting loop. In this study, we characterise an engineered variant of transthyretin, Ala108Tyr/Leu110Glu, which is kinetically and thermodynamically more stable than wild-type transthyretin, and as a consequence less amyloidogenic. Crystal structures of the mutant were determined in two space groups, P2(1)2(1)2 and C2, from crystals grown in the same crystallisation set-up. The structures are identical with the exception for residues Leu55-Leu58, situated at beta-strand D and the following DE loop. In particular, residues Leu55-His56 display large shifts in the C2 structure. There the direct hydrogen bonding between beta-strands D and A has been disrupted and is absent, whereas the beta-strand D is present in the P2(1)2(1)2 structure. This difference shows that from a mixture of metastable TTR molecules, only the molecules with an intact beta-strand D are selected for crystal growth in space group P2(1)2(1)2. The packing of TTR molecules in the C2 crystal form and in the previously determined amyloid TTR (ATTR) Leu55Pro crystal structure is close-to-identical. This packing arrangement is therefore not unique in amyloidogenic mutants of TTR.
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
1SOQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The beta-strand D of transthyretin trapped in two discrete conformations., Hornberg A, Olofsson A, Eneqvist T, Lundgren E, Sauer-Eriksson AE, Biochim Biophys Acta. 2004 Jul 1;1700(1):93-104. PMID:15210129
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