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| | ==Human Hsp27 core domain in complex with C-terminal peptide== | | ==Human Hsp27 core domain in complex with C-terminal peptide== |
| - | <StructureSection load='4mjh' size='340' side='right' caption='[[4mjh]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='4mjh' size='340' side='right'caption='[[4mjh]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4mjh]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MJH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MJH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4mjh]] is a 4 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=4MJH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MJH FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP27, HSP28, HSPB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.599Å</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=4mjh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mjh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mjh RCSB], [http://www.ebi.ac.uk/pdbsum/4mjh 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=4mjh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mjh OCA], [https://pdbe.org/4mjh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mjh RCSB], [https://www.ebi.ac.uk/pdbsum/4mjh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mjh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/HSPB1_HUMAN HSPB1_HUMAN]] Autosomal dominant Charcot-Marie-Tooth disease type 2F;Distal hereditary motor neuropathy type 2. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/HSPB1_HUMAN HSPB1_HUMAN] Autosomal dominant Charcot-Marie-Tooth disease type 2F;Distal hereditary motor neuropathy type 2. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HSPB1_HUMAN HSPB1_HUMAN]] Involved in stress resistance and actin organization. | + | [https://www.uniprot.org/uniprot/HSPB1_HUMAN HSPB1_HUMAN] Involved in stress resistance and actin organization. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Mammalian small heat-shock proteins (sHSPs) are molecular chaperones that form polydisperse and dynamic complexes with target proteins, serving as a first line of defense in preventing their aggregation into either amorphous deposits or amyloid fibrils. Their apparently broad target specificity makes sHSPs attractive for investigating ways to tackle disorders of protein aggregation. The two most abundant sHSPs in human tissue are alphaB-crystallin (ABC) and HSP27; here we present high-resolution structures of their core domains (cABC, cHSP27), each in complex with a segment of their respective C-terminal regions. We find that both truncated proteins dimerize, and although this interface is labile in the case of cABC, in cHSP27 the dimer can be cross-linked by an intermonomer disulfide linkage. Using cHSP27 as a template, we have designed an equivalently locked cABC to enable us to investigate the functional role played by oligomerization, disordered N and C termini, subunit exchange, and variable dimer interfaces in ABC. We have assayed the ability of the different forms of ABC to prevent protein aggregation in vitro. Remarkably, we find that cABC has chaperone activity comparable to that of the full-length protein, even when monomer dissociation is restricted through disulfide linkage. Furthermore, cABC is a potent inhibitor of amyloid fibril formation and, by slowing the rate of its aggregation, effectively reduces the toxicity of amyloid-beta peptide to cells. Overall we present a small chaperone unit together with its atomic coordinates that potentially enables the rational design of more effective chaperones and amyloid inhibitors.
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| - | The structured core domain of alphaB-crystallin can prevent amyloid fibrillation and associated toxicity.,Hochberg GK, Ecroyd H, Liu C, Cox D, Cascio D, Sawaya MR, Collier MP, Stroud J, Carver JA, Baldwin AJ, Robinson CV, Eisenberg DS, Benesch JL, Laganowsky A Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):E1562-70. doi:, 10.1073/pnas.1322673111. Epub 2014 Apr 7. PMID:24711386<ref>PMID:24711386</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | ==See Also== |
| - | </div>
| + | *[[Heat Shock Protein structures|Heat Shock Protein structures]] |
| - | == References == | + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Cascio, D]] | + | [[Category: Large Structures]] |
| - | [[Category: Eisenberg, D]] | + | [[Category: Cascio D]] |
| - | [[Category: Laganowsky, A]] | + | [[Category: Eisenberg D]] |
| - | [[Category: Sawaya, M R]] | + | [[Category: Laganowsky A]] |
| - | [[Category: Amyloid]] | + | [[Category: Sawaya MR]] |
| - | [[Category: Cancer]]
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| - | [[Category: Chaperone]]
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| - | [[Category: Small heat shock protein]]
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