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| | ==Structure of human serum amyloid A1== | | ==Structure of human serum amyloid A1== |
| - | <StructureSection load='4ip8' size='340' side='right' caption='[[4ip8]], [[Resolution|resolution]] 2.19Å' scene=''> | + | <StructureSection load='4ip8' size='340' side='right'caption='[[4ip8]], [[Resolution|resolution]] 2.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ip8]] 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=4IP8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IP8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ip8]] 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=4IP8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IP8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P4C:O-ACETALDEHYDYL-HEXAETHYLENE+GLYCOL'>P4C</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P4C:O-ACETALDEHYDYL-HEXAETHYLENE+GLYCOL'>P4C</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ip9|4ip9]]</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=4ip8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ip8 OCA], [https://pdbe.org/4ip8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ip8 RCSB], [https://www.ebi.ac.uk/pdbsum/4ip8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ip8 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SAA1 ([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=4ip8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ip8 OCA], [http://pdbe.org/4ip8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ip8 RCSB], [http://www.ebi.ac.uk/pdbsum/4ip8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ip8 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/SAA1_HUMAN SAA1_HUMAN]] Secondary amyloidosis. Reactive, secondary amyloidosis is characterized by the extracellular accumulation in various tissues of the SAA1 protein. These deposits are highly insoluble and resistant to proteolysis; they disrupt tissue structure and compromise function. Elevated serum SAA1 protein levels may be associated with lung cancer. | + | [https://www.uniprot.org/uniprot/SAA1_HUMAN SAA1_HUMAN] Secondary amyloidosis. Reactive, secondary amyloidosis is characterized by the extracellular accumulation in various tissues of the SAA1 protein. These deposits are highly insoluble and resistant to proteolysis; they disrupt tissue structure and compromise function. Elevated serum SAA1 protein levels may be associated with lung cancer. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SAA1_HUMAN SAA1_HUMAN]] Major acute phase reactant. Apolipoprotein of the HDL complex. | + | [https://www.uniprot.org/uniprot/SAA1_HUMAN SAA1_HUMAN] Major acute phase reactant. Apolipoprotein of the HDL complex. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lu, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Sun, P D]] | + | [[Category: Lu J]] |
| - | [[Category: Four-helix bundle]] | + | [[Category: Sun PD]] |
| - | [[Category: Human serum]]
| + | |
| - | [[Category: Main constituent of secondary amyloid]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Secondary amyloid]]
| + | |
| - | [[Category: Toll like receptor]]
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| Structural highlights
Disease
SAA1_HUMAN Secondary amyloidosis. Reactive, secondary amyloidosis is characterized by the extracellular accumulation in various tissues of the SAA1 protein. These deposits are highly insoluble and resistant to proteolysis; they disrupt tissue structure and compromise function. Elevated serum SAA1 protein levels may be associated with lung cancer.
Function
SAA1_HUMAN Major acute phase reactant. Apolipoprotein of the HDL complex.
Publication Abstract from PubMed
Serum amyloid A (SAA) represents an evolutionarily conserved family of inflammatory acute-phase proteins. It is also a major constituent of secondary amyloidosis. To understand its function and structural transition to amyloid, we determined a structure of human SAA1.1 in two crystal forms, representing a prototypic member of the family. Native SAA1.1 exists as a hexamer, with subunits displaying a unique four-helix bundle fold stabilized by its long C-terminal tail. Structure-based mutational studies revealed two positive-charge clusters, near the center and apex of the hexamer, that are involved in SAA association with heparin. The binding of high-density lipoprotein involves only the apex region of SAA and can be inhibited by heparin. Peptide amyloid formation assays identified the N-terminal helices 1 and 3 as amyloidogenic peptides of SAA1.1. Both peptides are secluded in the hexameric structure of SAA1.1, suggesting that the native SAA is nonpathogenic. Furthermore, dissociation of the SAA hexamer appears insufficient to initiate amyloidogenic transition, and proteolytic cleavage or removal of the C-terminal tail of SAA resulted in formation of various-sized structural aggregates containing approximately 5-nm regular repeating protofibril-like units. The combined structural and functional studies provide mechanistic insights into the pathogenic contribution of glycosaminoglycan in SAA1.1-mediated AA amyloid formation.
Structural mechanism of serum amyloid A-mediated inflammatory amyloidosis.,Lu J, Yu Y, Zhu I, Cheng Y, Sun PD Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5189-94. doi:, 10.1073/pnas.1322357111. Epub 2014 Mar 24. PMID:24706838[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lu J, Yu Y, Zhu I, Cheng Y, Sun PD. Structural mechanism of serum amyloid A-mediated inflammatory amyloidosis. Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5189-94. doi:, 10.1073/pnas.1322357111. Epub 2014 Mar 24. PMID:24706838 doi:http://dx.doi.org/10.1073/pnas.1322357111
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