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

肉毒梭菌神经毒素（Mr.150kDa）与培养物或食物中的无毒成分结合，形成大型复合物，称为12S (300 kDa), 16S （500 kDa）和19S （900 kDa）祖毒素。A型菌株产生12S、16S和19S三种毒素，B、C和D型菌株产生12S和16S两种毒素。E型、F型和G型只产生一种毒素；E型和F型产生12S毒素，G型产生16毒素。12S毒素由一种神经毒素和一种无毒成分组成，没有血凝素（HA）活性，这里称为NTNH。16S和19S毒素是12S毒素与HA结合形成的。通过遗传分析和蛋白质化学分析阐明了祖毒素的结构。结果表明：1)任何类型的ha均由4个亚组分组成，53,33,22-23和17 kDa，它们以1:2:1:1的比例相关；2)22-2 kDa亚组分由几种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组成。假设19S毒素是由HA-33交联的16S毒素的二聚体，4)a、C、D型毒素的ntnh在其n端区域有切割，在SDS-PAGE上被分成两部分。A型、C型、D型、E型和F型的ntnh的n端区域的多重比对表明，切割发生在一个包含短重复序列的区域，而只产生12S毒素的E型和F型缺少该区域。人们认为，NTNH中的加工是12S和16S（和19S）毒素在同一培养物中存在的原因，5)红细胞对HA的受体因毒素的类型而异；A和B毒素与中性脂结合，而C和D毒素与唾液酸结合在糖脂（如GM3和唾液酰副叶皂苷）和糖蛋白（如糖蛋白）中，6)C型HA的四种亚成分中HA-33和HA-53对红细胞具有结合活性，7)HA对祖毒素与小肠上皮细胞结合起重要作用。与ha阴性毒素相比，小肠更能有效吸收ha阳性毒素。少

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