Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
BMC Mol Cell Biol. 2021 Jan 7;22(1):4. doi: 10.1186/s12860-020-00338-2.
Pathogenesis of Helicobacter Pylori (HP) vacuolating toxin A (vacA) depends on polymorphic diversity within the signal (s), middle (m), intermediate (i), deletion (d) and c-regions. These regions show distinct allelic diversity. The s-region, m-region and the c-region (a 15 bp deletion at the 3'-end region of the p55 domain of the vacA gene) exist as 2 types (s1, s2, m1, m2, c1 and c2), while the i-region has 3 allelic types (i1, i2 and i3). The locus of d-region of the vacA gene has also been classified into 2 genotypes, namely d1 and d2. We investigated the "d-region"/"loop region" through bioinformatics, to predict its properties and relation to disease. One thousand two hundred fifty-nine strains from the NCBI nucleotide database and the dryad database with complete vacA sequences were included in the study. The sequences were aligned using BioEdit and analyzed using Lasergene and BLAST. The secondary structure and physicochemical properties of the region were predicted using PredictProtein.
We identified 31 highly polymorphic genotypes in the "d-region", with a mean length of 34 amino acids (9 ~ 55 amino acids). We further classified the 31 genotypes into 3 main types, namely K-type (strains starting with the KDKP motif in the "d-region"), Q-type (strains starting with the KNQT motif), and E-type (strains starting with the ESKT motif) respectively. The most common type, K-type, is more prevalent in cancer patients (80.87%) and is associated with the s1i1m1c1 genotypes (P < .01). Incidentally, a new region expressing sequence diversity (2 aa deletion) at the C-terminus of the p55 domain of vacA was identified during bioinformatics analysis.
Prediction of secondary structures shows that the "d-region" adopts a loop conformation and is a disordered region.
幽门螺杆菌（HP）空泡毒素 A（vacA）的发病机制取决于信号（s）、中间（m）、中间（i）、缺失（d）和 c 区的多态性多样性。这些区域显示出明显的等位基因多样性。s 区、m 区和 c 区（p55 结构域 3'末端区域的 15bp 缺失）存在 2 种类型（s1、s2、m1、m2、c1 和 c2），而 i 区有 3 种等位基因类型（i1、i2 和 i3）。vacA 基因 d 区的基因座也分为 2 种基因型，即 d1 和 d2。我们通过生物信息学研究了“d 区”/“环区”，以预测其性质及其与疾病的关系。研究纳入了来自 NCBI 核苷酸数据库和 Dryad 数据库的 1259 株具有完整 vacA 序列的菌株。使用 BioEdit 对齐序列，使用 Lasergene 和 BLAST 进行分析。使用 PredictProtein 预测该区域的二级结构和理化性质。
我们在“d 区”中鉴定出 31 种高度多态性基因型，平均长度为 34 个氨基酸（9-55 个氨基酸）。我们进一步将 31 种基因型分为 3 种主要类型，即 K 型（“d 区”以 KDKP 基序开头的菌株）、Q 型（以 KNQT 基序开头的菌株）和 E 型（以 ESKT 基序开头的菌株）。最常见的类型 K 型在癌症患者中更为常见（80.87%），与 s1i1m1c1 基因型相关（P<0.01）。顺便提一下，在生物信息学分析中发现了 vacA p55 结构域 C 末端表达序列多样性（2 个氨基酸缺失）的新区域。
二级结构预测表明，“d 区”采用环构象，是一个无序区域。
