1tij
From Proteopedia
(New page: 200px<br /> <applet load="1tij" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tij, resolution 3.03Å" /> '''3D Domain-swapped h...) |
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| - | [[Image:1tij.gif|left|200px]]<br /> | + | [[Image:1tij.gif|left|200px]]<br /><applet load="1tij" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1tij" size=" | + | |
caption="1tij, resolution 3.03Å" /> | caption="1tij, resolution 3.03Å" /> | ||
'''3D Domain-swapped human cystatin C with amyloid-like intermolecular beta-sheets'''<br /> | '''3D Domain-swapped human cystatin C with amyloid-like intermolecular beta-sheets'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Oligomerization of human cystatin C (HCC) leads to amyloid deposits in | + | Oligomerization of human cystatin C (HCC) leads to amyloid deposits in brain arteries, and this process is greatly accelerated with a naturally occurring L68Q variant. The crystal structures of N-truncated and full-length HCC (cubic form) showed dimer formation via three-dimensional (3D) domain swapping, and this observation has led to the suggestion that an analogous domain-swapping mechanism, but propagated in an open-ended fashion, could be the basis of HCC fibril formation. Here we report that full-length HCC, when crystallized in a new, tetragonal form, dimerizes by swapping the same secondary structure elements but with a very different overall structure generated by the flexibility of the hinge linking the moveable elements. The beta-strands of the beta-cores of the two folding units of the present dimer are roughly parallel, while they formed an angle of about 100 degrees in the previous two structures. The dimers pack around a crystallographic dyad by extending their molecular beta-sheets in an intermolecular context. At the other edge of the molecular beta-sheet, side-chain-side-chain hydrogen bonds propagate the beta-structure in the same direction. In consequence, a supramolecular crystal structure is generated, with all the beta-strands of the domain-swapped dimers being perpendicular to one crystallographic direction. This observation is relevant to amyloid aggregation of HCC, as X-ray diffraction studies of amyloid fibrils show them to have ordered, repeating structure, consistent with the so-called cross-beta structure, in which extended polypeptide chains are perpendicular to the fiber axis and form infinite beta-sheets that are parallel to this axis. |
==About this Structure== | ==About this Structure== | ||
| - | 1TIJ 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:// | + | 1TIJ 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=1TIJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: inhibitor of c1 and c13 cysteine proteases]] | [[Category: inhibitor of c1 and c13 cysteine proteases]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:13:51 2008'' |
Revision as of 13:13, 21 February 2008
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3D Domain-swapped human cystatin C with amyloid-like intermolecular beta-sheets
Overview
Oligomerization of human cystatin C (HCC) leads to amyloid deposits in brain arteries, and this process is greatly accelerated with a naturally occurring L68Q variant. The crystal structures of N-truncated and full-length HCC (cubic form) showed dimer formation via three-dimensional (3D) domain swapping, and this observation has led to the suggestion that an analogous domain-swapping mechanism, but propagated in an open-ended fashion, could be the basis of HCC fibril formation. Here we report that full-length HCC, when crystallized in a new, tetragonal form, dimerizes by swapping the same secondary structure elements but with a very different overall structure generated by the flexibility of the hinge linking the moveable elements. The beta-strands of the beta-cores of the two folding units of the present dimer are roughly parallel, while they formed an angle of about 100 degrees in the previous two structures. The dimers pack around a crystallographic dyad by extending their molecular beta-sheets in an intermolecular context. At the other edge of the molecular beta-sheet, side-chain-side-chain hydrogen bonds propagate the beta-structure in the same direction. In consequence, a supramolecular crystal structure is generated, with all the beta-strands of the domain-swapped dimers being perpendicular to one crystallographic direction. This observation is relevant to amyloid aggregation of HCC, as X-ray diffraction studies of amyloid fibrils show them to have ordered, repeating structure, consistent with the so-called cross-beta structure, in which extended polypeptide chains are perpendicular to the fiber axis and form infinite beta-sheets that are parallel to this axis.
About this Structure
1TIJ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
3D domain-swapped human cystatin C with amyloidlike intermolecular beta-sheets., Janowski R, Kozak M, Abrahamson M, Grubb A, Jaskolski M, Proteins. 2005 Nov 15;61(3):570-8. PMID:16170782
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