4ip9 | pdb_00004ip9

Structure of native human serum amyloid A1

spinqualitylabelsall models 4ip9, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ip9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: P4C Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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