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1g96

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HUMAN CYSTATIN C; DIMERIC FORM WITH 3D DOMAIN SWAPPING

Structural highlights

1g96 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:	,
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

The crystal structure of human cystatin C, a protein with amyloidogenic properties and a potent inhibitor of cysteine proteases, reveals how the protein refolds to produce very tight two-fold symmetric dimers while retaining the secondary structure of the monomeric form. The dimerization occurs through three-dimensional domain swapping, a mechanism for forming oligomeric proteins. The reconstituted monomer-like domains are similar to chicken cystatin except for one inhibitory loop that unfolds to form the 'open interface' of the dimer. The structure explains the tendency of human cystatin C to dimerize and suggests a mechanism for its aggregation in the brain arteries of elderly people with amyloid angiopathy. A more severe 'conformational disease' is associated with the L68Q mutant of human cystatin C, which causes massive amyloidosis, cerebral hemorrhage and death in young adults. The structure of the three-dimensional domain-swapped dimers shows how the L68Q mutation destabilizes the monomers and makes the partially unfolded intermediate less unstable. Higher aggregates may arise through the three-dimensional domain-swapping mechanism occurring in an open-ended fashion in which partially unfolded molecules are linked into infinite chains.

Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping.,Janowski R, Kozak M, Jankowska E, Grzonka Z, Grubb A, Abrahamson M, Jaskolski M Nat Struct Biol. 2001 Apr;8(4):316-20. PMID:11276250^[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, Jankowska E, Grzonka Z, Grubb A, Abrahamson M, Jaskolski M. Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping. Nat Struct Biol. 2001 Apr;8(4):316-20. PMID:11276250 doi:10.1038/86188

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/1g96"

@@ Line 1: / Line 1: @@
 ==HUMAN CYSTATIN C; DIMERIC FORM WITH 3D DOMAIN SWAPPING==
-<StructureSection load='1g96' size='340' side='right' caption='[[1g96]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+<StructureSection load='1g96' size='340' side='right'caption='[[1g96]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1g96]] is a 1 chain structure with 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=1G96 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1G96 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1g96]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G96 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1G96 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cew|1cew]], [[1stf|1stf]], [[1a67|1a67]], [[1dvc|1dvc]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1g96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g96 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1g96 RCSB], [http://www.ebi.ac.uk/pdbsum/1g96 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1g96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g96 OCA], [https://pdbe.org/1g96 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g96 RCSB], [https://www.ebi.ac.uk/pdbsum/1g96 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g96 ProSAT]</span></td></tr>
-<table>
+</table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/CYTC_HUMAN CYTC_HUMAN]] Defects in CST3 are the cause of amyloidosis type 6 (AMYL6) [MIM:[http://omim.org/entry/105150 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.<ref>PMID:2541223</ref> <ref>PMID:1352269</ref>   Genetic variations in CST3 are associated with age-related macular degeneration type 11 (ARMD11) [MIM:[http://omim.org/entry/611953 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.<ref>PMID:11815350</ref>
+[https://www.uniprot.org/uniprot/CYTC_HUMAN CYTC_HUMAN] Defects in CST3 are the cause of amyloidosis type 6 (AMYL6) [MIM:[https://omim.org/entry/105150 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.<ref>PMID:2541223</ref> <ref>PMID:1352269</ref>   Genetic variations in CST3 are associated with age-related macular degeneration type 11 (ARMD11) [MIM:[https://omim.org/entry/611953 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.<ref>PMID:11815350</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/CYTC_HUMAN 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.
+[https://www.uniprot.org/uniprot/CYTC_HUMAN 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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g9/1g96_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g9/1g96_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1g96 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 29: / Line 30: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1g96" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 34: / Line 36: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Abrahamson, M.]]
+[[Category: Large Structures]]
-[[Category: Grubb, A.]]
+[[Category: Abrahamson M]]
-[[Category: Grzonka, Z.]]
+[[Category: Grubb A]]
-[[Category: Jankowska, E.]]
+[[Category: Grzonka Z]]
-[[Category: Janowski, R.]]
+[[Category: Jankowska E]]
-[[Category: Jaskolski, M.]]
+[[Category: Janowski R]]
-[[Category: Kozak, M.]]
+[[Category: Jaskolski M]]
-[[Category: 3d domain swapping]]
+[[Category: Kozak M]]
-[[Category: Amyloid angiopathy and cerebral hemorrhage]]
-[[Category: Amyloid formation]]
-[[Category: Human cystatin c dimer]]
-[[Category: Hydrolase inhibitor]]
-[[Category: Inhibitor of c1 and c13 cysteine protease]]

1g96

From Proteopedia

Current revision

HUMAN CYSTATIN C; DIMERIC FORM WITH 3D DOMAIN SWAPPING

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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