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PDBsum entry 1tij

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protein Protein-protein interface(s) links
Hydrolase inhibitor PDB id
1tij
Jmol
Contents
Protein chains
114 a.a. *
Waters ×22
* Residue conservation analysis
PDB id:
1tij
Name: Hydrolase inhibitor
Title: 3d domain-swapped human cystatin c with amyloid-like intermolecular beta-sheets
Structure: Cystatin c. Chain: a, b. Synonym: gamma-trace, post-gamma-globulin. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cst3. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
3.03Å     R-factor:   0.217     R-free:   0.262
Authors: R.Janowski,M.Kozak,M.Abrahamson,A.Grubb,M.Jaskolski
Key ref:
R.Janowski et al. (2005). 3D domain-swapped human cystatin C with amyloidlike intermolecular beta-sheets. Proteins, 61, 570-578. PubMed id: 16170782 DOI: 10.1002/prot.20633
Date:
02-Jun-04     Release date:   19-Jul-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P01034  (CYTC_HUMAN) -  Cystatin-C
Seq:
Struc:
146 a.a.
114 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   14 terms 
  Biological process     cell activation   35 terms 
  Biochemical function     protein binding     6 terms  

 

 
DOI no: 10.1002/prot.20633 Proteins 61:570-578 (2005)
PubMed id: 16170782  
 
 
3D domain-swapped human cystatin C with amyloidlike intermolecular beta-sheets.
R.Janowski, M.Kozak, M.Abrahamson, A.Grubb, M.Jaskolski.
 
  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.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Interactions of the 3D domain-swapped dimers of tetragonal HCC at the edges of the molecular -sheets. An HCC tetramer, formed from two dimers (AB, blue and green, and a symmetry-related dimer A B , red and yellow) via two systems of parallel -interactions between the 5-strands (a). Each of the 5- 5 motifs, shown in a 2F[o]-F[c] map (contour level 1.1 ), includes five main-chain-main-chain hydrogen bonds (b). At the other edges of the -sheets, neighboring dimers interact via side-chain-side-chain hydrogen bonding between their 2-chains, shown in a 2F[o]-F[c] map contoured at the 1.1 level (c).
Figure 3.
Figure 3. Packing of the domain-swapped HCC dimers in the tetragonal crystal form. In the center, a tetramer formed from two dimers (blue/green and red/yellow) by 5- 5 interactions is shown, as in Figure 2(a). The tetramers in the upper and lower layers are connected to the central unit via 2- 2 interactions, as in Figure 2(c). This system of interactions extends in three dimentions and encompasses the entire crystal.
 
  The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2005, 61, 570-578) copyright 2005.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19898742 A.Rostagno, J.L.Holton, T.Lashley, T.Revesz, and J.Ghiso (2010).
Cerebral amyloidosis: amyloid subunits, mutants and phenotypes.
  Cell Mol Life Sci, 67, 581-600.  
20545851 M.Kotsyfakis, H.Horka, J.Salat, and J.F.Andersen (2010).
The crystal structures of two salivary cystatins from the tick Ixodes scapularis and the effect of these inhibitors on the establishment of Borrelia burgdorferi infection in a murine model.
  Mol Microbiol, 77, 456-470.
PDB codes: 3lh4 3li7 3mwz
20175878 R.Kolodziejczyk, K.Michalska, A.Hernandez-Santoyo, M.Wahlbom, A.Grubb, and M.Jaskolski (2010).
Crystal structure of human cystatin C stabilized against amyloid formation.
  FEBS J, 277, 1726-1737.
PDB code: 3gax
20091872 R.P.Nagarkar, R.A.Hule, D.J.Pochan, and J.P.Schneider (2010).
Domain swapping in materials design.
  Biopolymers, 94, 141-155.  
17763469 G.Cozza, S.Moro, and G.Gotte (2008).
Elucidation of the ribonuclease A aggregation process mediated by 3D domain swapping: a computational approach reveals possible new multimeric structures.
  Biopolymers, 89, 26-39.  
18537545 U.Baxa (2008).
Structural basis of infectious and non-infectious amyloids.
  Curr Alzheimer Res, 5, 308-318.  
17996039 I.Pallarés, C.Berenguer, F.X.Avilés, J.Vendrell, and S.Ventura (2007).
Self-assembly of human latexin into amyloid-like oligomers.
  BMC Struct Biol, 7, 75.  
17470433 M.Wahlbom, X.Wang, V.Lindström, E.Carlemalm, M.Jaskolski, and A.Grubb (2007).
Fibrillogenic oligomers of human cystatin C are formed by propagated domain swapping.
  J Biol Chem, 282, 18318-18326.  
17433843 T.Cellmer, D.Bratko, J.M.Prausnitz, and H.W.Blanch (2007).
Protein aggregation in silico.
  Trends Biotechnol, 25, 254-261.  
17439156 Y.M.Lin, H.L.Liu, J.H.Zhao, C.H.Huang, H.W.Fang, Y.Ho, and W.Y.Chen (2007).
Molecular dynamics simulations to investigate the domain swapping mechanism of human cystatin C.
  Biotechnol Prog, 23, 577-584.  
16612983 E.Levy, M.Jaskolski, and A.Grubb (2006).
The role of cystatin C in cerebral amyloid angiopathy and stroke: cell biology and animal models.
  Brain Pathol, 16, 60-70.  
16698543 M.J.Bennett, M.R.Sawaya, and D.Eisenberg (2006).
Deposition diseases and 3D domain swapping.
  Structure, 14, 811-824.  
17107883 S.D.Khare, M.Caplow, and N.V.Dokholyan (2006).
FALS mutations in Cu, Zn superoxide dismutase destabilize the dimer and increase dimer dissociation propensity: a large-scale thermodynamic analysis.
  Amyloid, 13, 226-235.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.