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1TIJ

3D Domain-swapped human cystatin C with amyloid-like intermolecular beta-sheets

Summary for 1TIJ
Entry DOI10.2210/pdb1tij/pdb
Related1A67 1CEW 1DVC 1G96 1N9J 1R4C 1RN7 1STF
DescriptorCystatin C (2 entities in total)
Functional Keywordshuman cystatin c dimer, 3d domain swapping, amyloid formation, inhibitor of c1 and c13 cysteine proteases, amyloid angiopathy, cerebral hemorrhage, hydrolase inhibitor
Biological sourceHomo sapiens (human)
Cellular locationSecreted: P01034
Total number of polymer chains2
Total formula weight26730.28
Authors
Janowski, R.,Kozak, M.,Abrahamson, M.,Grubb, A.,Jaskolski, M. (deposition date: 2004-06-02, release date: 2005-07-19, Last modification date: 2024-10-16)
Primary citationJanowski, R.,Kozak, M.,Abrahamson, M.,Grubb, A.,Jaskolski, M.
3D domain-swapped human cystatin C with amyloidlike intermolecular beta-sheets.
Proteins, 61:570-578, 2005
Cited by
PubMed Abstract: 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.
PubMed: 16170782
DOI: 10.1002/prot.20633
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (3.03 Å)
Structure validation

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数据于2025-02-05公开中

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