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1tij

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Revision as of 08:51, 21 March 2018

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

Structural highlights

1tij is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1g96, 1r4c, 1cew, 1stf, 1rn7, 1a67, 1dvc, 1n9j
Gene:	CST3 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CYTC_HUMAN] Defects in CST3 are the cause of amyloidosis type 6 (AMYL6) [MIM:105150]; also known as hereditary cerebral hemorrhage with amyloidosis (HCHWA), cerebral amyloid angiopathy (CAA) or cerebroarterial amyloidosis Icelandic type. AMYL6 is a hereditary generalized amyloidosis due to cystatin C amyloid deposition. Cystatin C amyloid accumulates in the walls of arteries, arterioles, and sometimes capillaries and veins of the brain, and in various organs including lymphoid tissue, spleen, salivary glands, and seminal vesicles. Amyloid deposition in the cerebral vessels results in cerebral amyloid angiopathy, cerebral hemorrhage and premature stroke. Cystatin C levels in the cerebrospinal fluid are abnormally low.^[1] ^[2] Genetic variations in CST3 are associated with age-related macular degeneration type 11 (ARMD11) [MIM:611953]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.^[3]

Function

[CYTC_HUMAN] As an inhibitor of cysteine proteinases, this protein is thought to serve an important physiological role as a local regulator of this enzyme activity.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Levy E, Lopez-Otin C, Ghiso J, Geltner D, Frangione B. Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteases. J Exp Med. 1989 May 1;169(5):1771-8. PMID:2541223
↑ Abrahamson M, Jonsdottir S, Olafsson I, Jensson O, Grubb A. Hereditary cystatin C amyloid angiopathy: identification of the disease-causing mutation and specific diagnosis by polymerase chain reaction based analysis. Hum Genet. 1992 Jun;89(4):377-80. PMID:1352269
↑ Zurdel J, Finckh U, Menzer G, Nitsch RM, Richard G. CST3 genotype associated with exudative age related macular degeneration. Br J Ophthalmol. 2002 Feb;86(2):214-9. PMID:11815350
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1tij"

@@ Line 1: / Line 1: @@
 ==3D Domain-swapped human cystatin C with amyloid-like intermolecular beta-sheets==
 <StructureSection load='1tij' size='340' side='right' caption='[[1tij]], [[Resolution|resolution]] 3.03&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1g96|1g96]], [[1r4c|1r4c]], [[1cew|1cew]], [[1stf|1stf]], [[1rn7|1rn7]], [[1a67|1a67]], [[1dvc|1dvc]], [[1n9j|1n9j]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CST3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tij FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tij OCA], [http://pdbe.org/1tij PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tij RCSB], [http://www.ebi.ac.uk/pdbsum/1tij PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tij FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tij OCA], [http://pdbe.org/1tij PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tij RCSB], [http://www.ebi.ac.uk/pdbsum/1tij PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1tij ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ti/1tij_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ti/1tij_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1tij

From Proteopedia

Revision as of 08:51, 21 March 2018

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

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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