First time at Proteopedia? Click on the green links: they change the 3D image. Click and drag the molecules. Proteopedia is a 3D, interactive encyclopedia of proteins, RNA, DNA and other molecules. With a free user account, you can edit pages in Proteopedia. Visit the Main Page to learn more.
1tij
From Proteopedia
| 1tij, resolution 3.03Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Gene: | CST3 (Homo sapiens) | ||||||||
| Domains: | CY | ||||||||
| Related: | 1g96, 1r4c, 1cew, 1stf, 1rn7, 1a67, 1dvc, 1n9j | ||||||||
| |||||||||
| |||||||||
| |||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
3D Domain-swapped human cystatin C with amyloid-like intermolecular beta-sheets
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1TIJ is a 2 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Janowski R, Kozak M, Abrahamson M, Grubb A, Jaskolski M. 3D domain-swapped human cystatin C with amyloidlike intermolecular beta-sheets. Proteins. 2005 Nov 15;61(3):570-8. PMID:16170782 doi:10.1002/prot.20633
Page seeded by OCA on Tue Feb 17 15:03:25 2009
