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| | ==Solution Structure of the 3D domain swapped dimer of Stefin A== | | ==Solution Structure of the 3D domain swapped dimer of Stefin A== |
| - | <StructureSection load='1n9j' size='340' side='right' caption='[[1n9j]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='1n9j' size='340' side='right'caption='[[1n9j]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1n9j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N9J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1N9J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1n9j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N9J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N9J FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dvc|1dvc]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1n9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n9j OCA], [http://pdbe.org/1n9j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1n9j RCSB], [http://www.ebi.ac.uk/pdbsum/1n9j 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=1n9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n9j OCA], [https://pdbe.org/1n9j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n9j RCSB], [https://www.ebi.ac.uk/pdbsum/1n9j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n9j ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CYTA_HUMAN CYTA_HUMAN]] Defects in CSTA are the cause of ichthyosis exfoliative autosomal recessive ichthyosis bullosa of Siemens-like (AREI) [MIM:[http://omim.org/entry/607936 607936]]. A form of congenital exfoliative ichthyosis, sharing some features with ichthyosis bullosa of Siemens and annular epidermolytic ichthyosis. AREI presents shortly after birth as dry, scaly skin over most of the body with coarse peeling of non-erythematous skin on the palms and soles, which is exacerbated by excessive moisture and minor trauma. Electron microscopy analysis of skin biopsies, reveals mostly normal-appearing upper layers of the epidermis, but prominent intercellular edema of the basal and suprabasal cell layers with aggregates of tonofilaments in the basal keratinocytes.<ref>PMID:21944047</ref> | + | [https://www.uniprot.org/uniprot/CYTA_HUMAN CYTA_HUMAN] Defects in CSTA are the cause of ichthyosis exfoliative autosomal recessive ichthyosis bullosa of Siemens-like (AREI) [MIM:[https://omim.org/entry/607936 607936]. A form of congenital exfoliative ichthyosis, sharing some features with ichthyosis bullosa of Siemens and annular epidermolytic ichthyosis. AREI presents shortly after birth as dry, scaly skin over most of the body with coarse peeling of non-erythematous skin on the palms and soles, which is exacerbated by excessive moisture and minor trauma. Electron microscopy analysis of skin biopsies, reveals mostly normal-appearing upper layers of the epidermis, but prominent intercellular edema of the basal and suprabasal cell layers with aggregates of tonofilaments in the basal keratinocytes.<ref>PMID:21944047</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CYTA_HUMAN CYTA_HUMAN]] This is an intracellular thiol proteinase inhibitor. Has an important role in desmosome-mediated cell-cell adhesion in the lower levels of the epidermis.<ref>PMID:21944047</ref> | + | [https://www.uniprot.org/uniprot/CYTA_HUMAN CYTA_HUMAN] This is an intracellular thiol proteinase inhibitor. Has an important role in desmosome-mediated cell-cell adhesion in the lower levels of the epidermis.<ref>PMID:21944047</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n9/1n9j_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n9/1n9j_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </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=1n9j ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Conroy, M J]] | + | [[Category: Large Structures]] |
| - | [[Category: Craven, C J]] | + | [[Category: Conroy MJ]] |
| - | [[Category: Giannini, S]] | + | [[Category: Craven CJ]] |
| - | [[Category: Higgins, L D]] | + | [[Category: Giannini S]] |
| - | [[Category: Hounslow, A M]] | + | [[Category: Higgins LD]] |
| - | [[Category: Jerala, R]] | + | [[Category: Hounslow AM]] |
| - | [[Category: Staniforth, R A]] | + | [[Category: Jerala R]] |
| - | [[Category: Waltho, J P]] | + | [[Category: Staniforth RA]] |
| - | [[Category: Amyloid]]
| + | [[Category: Waltho JP]] |
| - | [[Category: Cystatin]]
| + | |
| - | [[Category: Domain swapped]]
| + | |
| - | [[Category: Hydrolase inhibitor]]
| + | |
| - | [[Category: Stefin some]]
| + | |
| Structural highlights
Disease
CYTA_HUMAN Defects in CSTA are the cause of ichthyosis exfoliative autosomal recessive ichthyosis bullosa of Siemens-like (AREI) [MIM:607936. A form of congenital exfoliative ichthyosis, sharing some features with ichthyosis bullosa of Siemens and annular epidermolytic ichthyosis. AREI presents shortly after birth as dry, scaly skin over most of the body with coarse peeling of non-erythematous skin on the palms and soles, which is exacerbated by excessive moisture and minor trauma. Electron microscopy analysis of skin biopsies, reveals mostly normal-appearing upper layers of the epidermis, but prominent intercellular edema of the basal and suprabasal cell layers with aggregates of tonofilaments in the basal keratinocytes.[1]
Function
CYTA_HUMAN This is an intracellular thiol proteinase inhibitor. Has an important role in desmosome-mediated cell-cell adhesion in the lower levels of the epidermis.[2]
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
Cystatins, an amyloid-forming structural superfamily, form highly stable, domain-swapped dimers at physiological protein concentrations. In chicken cystatin, the active monomer is a kinetic trap en route to dimerization, and any changes in solution conditions or mutations that destabilize the folded state shorten the lifetime of the monomeric form. In such circumstances, amyloidogenesis will start from conditions where a domain-swapped dimer is the most prevalent species. Domain swapping occurs by a rearrangement of loop I, generating the new intermonomer interface between strands 2 and 3. The transition state for dimerization has a high level of hydrophobic group exposure, indicating that gross conformational perturbation is required for domain swapping to occur. Dimerization also occurs when chicken cystatin is in its reduced, molten-globule state, implying that the organization of secondary structure in this state mirrors that in the folded state and that domain swapping is not limited to the folded states of proteins. Although the interface between cystatin-fold units is poorly defined for cystatin A, the dimers are the appropriate size to account for the electron-dense regions in amyloid protofilaments.
Three-dimensional domain swapping in the folded and molten-globule states of cystatins, an amyloid-forming structural superfamily.,Staniforth RA, Giannini S, Higgins LD, Conroy MJ, Hounslow AM, Jerala R, Craven CJ, Waltho JP EMBO J. 2001 Sep 3;20(17):4774-81. PMID:11532941[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Blaydon DC, Nitoiu D, Eckl KM, Cabral RM, Bland P, Hausser I, van Heel DA, Rajpopat S, Fischer J, Oji V, Zvulunov A, Traupe H, Hennies HC, Kelsell DP. Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell-cell adhesion. Am J Hum Genet. 2011 Oct 7;89(4):564-71. doi: 10.1016/j.ajhg.2011.09.001. Epub, 2011 Sep 22. PMID:21944047 doi:10.1016/j.ajhg.2011.09.001
- ↑ Blaydon DC, Nitoiu D, Eckl KM, Cabral RM, Bland P, Hausser I, van Heel DA, Rajpopat S, Fischer J, Oji V, Zvulunov A, Traupe H, Hennies HC, Kelsell DP. Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell-cell adhesion. Am J Hum Genet. 2011 Oct 7;89(4):564-71. doi: 10.1016/j.ajhg.2011.09.001. Epub, 2011 Sep 22. PMID:21944047 doi:10.1016/j.ajhg.2011.09.001
- ↑ Staniforth RA, Giannini S, Higgins LD, Conroy MJ, Hounslow AM, Jerala R, Craven CJ, Waltho JP. Three-dimensional domain swapping in the folded and molten-globule states of cystatins, an amyloid-forming structural superfamily. EMBO J. 2001 Sep 3;20(17):4774-81. PMID:11532941 doi:http://dx.doi.org/10.1093/emboj/20.17.4774
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