Structure and function of the nontoxic components of Clostridium botulinum progenitor toxins.

肉毒杆菌祖毒素无毒成分的结构和功能。

• 批准号: 08457088
• 负责人: OGUMA Keiji
• 金额: $ 4.03万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457088/
• 关键词: C.botulinum; botulinum toxin; nontoxic component; Hemagglutinin; ポツリヌス菌; ポツリヌス毒素

Clostridium botulinum neurotoxins (Mr.150kDa) associate with nontoxic components in the cultures or in the foods, and become large complexes designated 12S (300 kDa), 16S (500 kDa), and 19S (900 kDa) progenitor toxins. Type A strain produces three formes of toxins, 12S,16S,and 19S,and type B,C,and D produce two formes of toxins, 12S and16S.Types E,F and G produce only one type of toxin ; types E and F produce 12S toxin, and type G produces 16 toxin. The 12S toxin consists of a neurotoxin and a nontoxic component showing no hemagglutinin (HA) activity, described here as a NTNH.The 16S and 19S toxins are formed by conjugation of 12S toxin with HA.The structure of progenitor toxins was clarified by both genetic- and protein chemical- analyzes. The conclusions drawn are 1) any types of HAs consist of four subcomponents, 53,33,22-23, and 17 kDa, which associated in the ratio of 1 : 2 : 1 : 1,2) the 22-2 kDa subcomponent consists of several proteins having a slightly different Mr, 3) type A … More 19S and 16S toxins consist of the same protein components. It was postulated that the 19S toxin is a dimmer of the 16S toxin cross-linked by HA-33,4) the NTNHs of type A,C,and D 12S toxins have a cleavage on their N-terminal regions, and are separated into two parts on SDS-PAGE.A multiple alignment of N-terminal regions of the NTNHs of types A,C,D,E,and F demonstrated that the cleavage occurs in a region including a short repeat sequence, and that types E and F which produce only 12S toxin lack this region. It was thought that the processing in NTNH is the reason why the 12S and 16S (and 19S) toxins exist in the same culture, 5) the receptors of red blood cells for HA arre different depending on the types of toxins ; A and B toxins bind to neutral lipids, whereas C and D toxins bind to sialic acids in both glicolipids (such as GM3 and sialylparagloboside) and glycoproteins (such as glycophorin), 6) In type C,HA-33 and HA-53 out of four subcomponents of HA,have the binding activity to the erythrocytes, 7) HA plays an important role for the progenitor toxin to bind to the epithelial cells of small intestine, that leads to efficient absorption of the HA-positive toxins is small intestine s compared with the HA-negative toxin. Less

肉毒梭菌神经毒素(Mr 150 KDa)与培养物或食物中的无毒成分结合，形成12S(300 KDa)、16S(500 KDa)和19S(900 KDa)前体毒素的大复合体。A型菌株产生12S、16S和19S三种形式的毒素，B、C和D型产生12S和16S两种形式的毒素，E、F和G型只产生一种类型的毒素，E和F型产生12S毒素，G型产生16种毒素。12S毒素由一种神经毒素和一种不具有血凝素(HA)活性的无毒成分组成，称为NTNP。16S和19S毒素是由12S毒素与HA结合而成的。得出的结论是：1)任何类型的HAS都由53、33、22-23和17 kDa四个亚组分组成，它们的比例为1：2：1：1；2)22-2 kDa的亚组分由几个MR略有不同的蛋白质组成；3)A型…更多的19s和16s毒素由相同的蛋白质成分组成。推测19S毒素是由HA-33交联的16S毒素的二聚体。4)A、C和D型12S毒素的NTNH在其N-末端区域有裂解，并在SDS-PAGE上被分成两部分。A、C、D、E和F型NTNH的N-末端区域的多重比对表明，裂解发生在包含短重复序列的区域，而E和F型只产生12S毒素。认为12S和16S(和19S)毒素在同一培养物中存在的原因是NTNH的加工过程。5)红细胞对HA的受体因毒素类型不同而不同；A、B毒素与中性脂类结合，而C、D毒素与脂类(如GM3、唾液酸副糖苷)和糖蛋白(如血糖蛋白)结合；6)在HA的四个亚组分中，C型、HA-33和HA-53具有与红细胞结合的活性；7)HA在前体毒素与小肠上皮细胞结合中起重要作用，导致HA阳性毒素的有效吸收是小肠S。较少

项目成果

Moriishi, K., et al.: "Mosaic structures of neurotoxins produced from Clostridium botulinum types C and D organisms." Biochim.Biophys Acta.1307・2. 123-126 (1996)

Moriishi, K., et al.：“C 型和 D 型肉毒杆菌产生的神经毒素的镶嵌结构。Biochim.Biophys Acta.1307·2 (1996)。”

Oguma, K., et al.: "Pathogenicity of Clstridium botulinum" Journal of Medical technology. 41/6. 646-654 (1997)

Oguma, K. 等人：“肉毒杆菌的致病性”医学技术杂志。

小熊 惠二 他: "ボツリヌス毒素" 治療学. 31・12. 1467-1473 (1997)

Keiji Oguma 等：“肉毒杆菌毒素”治疗学 31・12（1997）。

Inoue, K., et al.: "Structure and fanction of Clostridium botulinum progenitor toxins." Protein, Nucleic Acid and Enzyme. 42/10. 2049-2060 (1997)

Inoue, K., et al.：“肉毒梭菌祖毒素的结构和作用。”

Moriishi,K.,et al.: "Mosaic atructures of neurotoxins produced from Clostridium botulinum types C and D organisms." Biochim.Biophys Acta.1307・2. 123-126 (1996)

Moriishi, K., et al.：“C 型和 D 型肉毒杆菌产生的神经毒素的镶嵌结构。”Biochim.Biophys Acta.1307·2 (1996)。