title: Serum amyloid A1: Structure, function and gene polymorphism.
abstract: Inducible expression of serum amyloid A (SAA) is a hallmark of the acute-phase response, which is a conserved reaction of vertebrates to environmental challenges such as tissue injury, infection and surgery. Human SAA1 is encoded by one of the four SAA genes and is the best-characterized SAA protein. Initially known as a major precursor of amyloid A (AA), SAA1 has been found to play an important role in lipid metabolism and contributes to bacterial clearance, the regulation of inflammation and tumor pathogenesis. SAA1 has five polymorphic coding alleles (SAA1.1-SAA1.5) that encode distinct proteins with minor amino acid substitutions. Single nucleotide polymorphism (SNP) has been identified in both the coding and non-coding regions of human SAA1. Despite high levels of sequence homology among these variants, SAA1 polymorphisms have been reported as risk factors of cardiovascular diseases and several types of cancer. A recently solved crystal structure of SAA1.1 reveals a hexameric bundle with each of the SAA1 subunits assuming a 4-helix structure stabilized by the C-terminal tail. Analysis of the native SAA1.1 structure has led to the identification of a competing site for high-density lipoprotein (HDL) and heparin, thus providing the structural basis for a role of heparin and heparan sulfate in the conversion of SAA1 to AA. In this brief review, we compares human SAA1 with other forms of human and mouse SAAs, and discuss how structural and genetic studies of SAA1 have advanced our understanding of the physiological functions of the SAA proteins.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China; Institute of Chinese Medical Sciences and State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau, SAR, China. Electronic address: richardye@umac.mo.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Ye
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020641:Polymorphism, Single Nucleotide; D000685:Serum Amyloid A Protein / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*
chemical_list: C521404:SAA1 protein, human; C489995:Saa2 protein, mouse; D000685:Serum Amyloid A Protein
keywords: Acute-phase response; Gene polymorphism; Induced expression; Inflammation; Lipid metabolism; Serum amyloid A