Human serum amyloid A (SAA): biosynthesis and postsynthetic processing of preSAA and structural variants defined by complementary DNA.

Human serum amyloid A (SAA): biosynthesis and postsynthetic processing of preSAA and structural variants defined by complementary DNA.
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人血清淀粉样蛋白 A (SAA):SAA 前体和由互补 DNA 定义的结构变体的生物合成和合成后加工。

DOI:
10.1021/bi00333a018
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发表时间:
1985
期刊:
影响因子:
2.9
通讯作者:
Whitehead,AS
Whitehead,AS
中科院分区:
生物学3区
文献类型:
--
作者:
Sipe,JD;Colten,HR;Goldberger,G;Edge,MD;Tack,BF;Cohen,AS;Whitehead,AS

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医学系、桑代克纪念实验室和关节炎中心,波士顿大学医学院,波士顿,马萨诸塞州 02118,细胞生物学部,医学部,儿童医院,Ina Sue Perlmutter 囊性纤维化研究中心和儿科,哈佛医学院,波士顿,马萨诸塞州 02115,制药部,帝国化学工业有限公司,梅里塞德,麦克尔斯菲尔德,柴郡,英格兰,和部门免疫学,Scripps Clinic and Research Foundation,La Jolla,California 92037 1984 年 8 月 30 日收到摘要:为了研究人血清淀粉样蛋白 A (SAA)(一种高密度脂蛋白的脱辅基蛋白)的结构变异,使用两种合成寡核苷酸混合物从人肝脏文库中分离出互补 DNA 克隆,其中含有可编码蛋白质序列残基 33-38 和 90-95 的序列。 SAA特异性cDNA克隆(pA1)含有编码成熟SAA的核苷酸序列和18个残基信号肽的10个氨基酸。它还包括一个 70 个核苷酸长的 3'-非翻译区和大约 120 个碱基的聚 (A) 尾。 pA1的衍生氨基酸序列与apoSAA1的α形式相同。含有SAA保守区(残基33-38)的pA1片段也与来自人急性期肝脏和急性期刺激但未刺激的小鼠和兔肝脏的RNA杂交。相反,对应于可变区的片段与人RNA的杂交程度比与兔或鼠RNA的杂交程度高得多。人急性期肝脏 SAA mRNA(长度约为 600 个核苷酸)在无细胞翻译系统中指导 preSAA (Mr 14000) 的合成。在非洲爪蟾卵母细胞翻译系统中,preSAA 被合成并加工成成熟的 Mr 12000 产品。 preSAA完整的18个氨基酸信号肽序列来源于SAA mRNA成熟产物氨基末端区域通过“引物延伸”合成的cDNA测序。两个其他SAA特异性cDNA克隆(pA6和pA10)与pA1的不同之处在于它们缺乏跨越pA1的残基54-56的内部Pst I限制酶位点。因此,在急性期反应期间至少有两种SAA基因产物被转录。 iSerum 淀粉样蛋白 A (SAA) 是两种主要的诱导性人类急性期蛋白之一。 SAA 因不溶性/3 折叠片状原纤维蛋白淀粉样蛋白 A (AA) 命名,该蛋白可能通过其氨基和羧基的蛋白水解而衍生自 SAA。
Department of Medicine, The ThorndikeMemorial Laboratory, and the Arthritis Center, Boston University School of Medicine, Boston, Massachusetts 02118, Division of Cell Biology, Department of Medicine, Children’s Hospital, Ina Sue Perlmutter Cystic Fibrosis Research Center, and the Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, Pharmaceuticals Division, Imperial Chemical Industries PLC, Mereside, Macclesfield, Cheshire, England, and Department of Immunology, Scripps Clinic andResearch Foundation, La Jolla, California 92037 Received August 30, 1984 abstract: To study structural variants of human serum amyloid A (SAA), an apoprotein of high-density lipoprotein, complementary DNA clones were isolated from a human liver library with the use of two synthetic oligonucleotide mixtures containing sequences that could code for residues 33-38 and 90-95 of the protein sequence. The SAA-specific cDNA clone (pAl) contains the nucleotide sequence coding for the mature SAA and 10 amino acids of the 18-residue signal peptide. It also includes a 70 nucleotide long 3'-untranslated region and approximately 120 bases of the poly (A) tail. The derived amino acid sequence of pAl is identical with the a form of apoSAAl. A fragment of pAl containing the conserved (residues 33-38) region of SAA also hybridized with RNA from humanacute phase liver and acute phase stimulated, but not unstimulated, mouse and rabbit liver. In contrast, a fragment correspondingto the variable region hybridized to a much greater extent with human than with rabbit or murine RNA. Human acute phase liver SAA mRNA (~ 600 nucleotides in length) directs synthesis of preSAA (Mr 14000) in a cell-free translating system. In a Xenopus oocyte translation system preSAA is synthesized and processed to the mature Mr 12000 product. The complete 18 amino acid signal peptide sequence of preSAA was derived from sequencing cDNA synthesized by “primer extension” from the region of SAA mRNA corresponding to the amino terminus of the mature product. Two other SAA-specific cDNA clones (pA6 and pAlO) differed from pAl in that they lack the internal Pst I restriction enzyme site spanning residues 54-56 of pAl. Thus, there are at least two SAA gene products transcribed during the acute phase response. iSerum amyloid A (SAA) is one of two major inducible human acute phase proteins. SAA is named for the insoluble/3-pleated sheet fibril protein amyloid A (AA) that is probably derived fromSAA by proteolysis at both its amino and car-