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1g96
From Proteopedia
(New page: 200px<br /> <applet load="1g96" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g96, resolution 2.5Å" /> '''HUMAN CYSTATIN C; DI...) |
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| - | [[Image:1g96.gif|left|200px]]<br /> | + | [[Image:1g96.gif|left|200px]]<br /><applet load="1g96" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1g96" size=" | + | |
caption="1g96, resolution 2.5Å" /> | caption="1g96, resolution 2.5Å" /> | ||
'''HUMAN CYSTATIN C; DIMERIC FORM WITH 3D DOMAIN SWAPPING'''<br /> | '''HUMAN CYSTATIN C; DIMERIC FORM WITH 3D DOMAIN SWAPPING'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of human cystatin C, a protein with amyloidogenic | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1G96 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1G96 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G96 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: inhibitor of c1 and c13 cysteine proteases]] | [[Category: inhibitor of c1 and c13 cysteine proteases]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:47:31 2008'' |
Revision as of 10:47, 21 February 2008
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HUMAN CYSTATIN C; DIMERIC FORM WITH 3D DOMAIN SWAPPING
Overview
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.
About this Structure
1G96 is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 12:47:31 2008
Categories: Homo sapiens | Single protein | Abrahamson, M. | Grubb, A. | Grzonka, Z. | Jankowska, E. | Janowski, R. | Jaskolski, M. | Kozak, M. | CL | GOL | 3d domain swapping | Amyloid angiopathy and cerebral hemorrhage | Amyloid formation | Human cystatin c dimer | Inhibitor of c1 and c13 cysteine proteases
